WO1999056537A2 - Biological pest control methods and compositions - Google Patents
Biological pest control methods and compositions Download PDFInfo
- Publication number
- WO1999056537A2 WO1999056537A2 PCT/NZ1999/000052 NZ9900052W WO9956537A2 WO 1999056537 A2 WO1999056537 A2 WO 1999056537A2 NZ 9900052 W NZ9900052 W NZ 9900052W WO 9956537 A2 WO9956537 A2 WO 9956537A2
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- Prior art keywords
- bait
- animal
- analogues
- antagonists
- adjuvant
- Prior art date
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- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/002—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits
- A01N25/006—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits insecticidal
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/002—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing a foodstuff as carrier or diluent, i.e. baits
Definitions
- the present invention relates to methods to increase the efficacy and acceptability of control methods. Also provided are baits and adjuvants useful in these methods.
- Pest animal species are responsible for significant environmental damage, as well as having deleterious effects on human activities such as forestry, horticulture, and agriculture. Animal species cover a plethora of both vertebrate and invertebrate species. Damage is caused by the pests in many different ways including: competing for food with farmed animals; damaging indigenous flora, especially through overgrazing; destroying indigenous animal species through predation; - damaging agricultural, horticultural and silvicultural crops through grazing; and acting as vectors for infectious agents.
- Baiting programmes are commonly employed to control a wide variety of biological pests.
- the bait will comprise a substance which an animal finds palatable or attractive and a toxic substance or an active substance otherwise having an effect on the animal, for example, a contraceptive agent.
- a common problem associated with bait programmes is the development in an animal population of bait aversion. Aversion develops when the animals consume a sub-lethal dose of the toxin, or other substance, through numerous mechanisms and then associates subsequent ill effects with the bait and/or toxin or active substance. As a result, the animal avoids the consumption of that bait. Techniques for addressing bait aversion are known in the art and discussed in the present applicants New Zealand Patent No. 260302.
- NZ 260302 addresses bait aversion in animals by disrupting the associative learning process using glutamate antagonists or agonists to block or disrupt the glutamate neurotransmitter pathway.
- the purpose of disrupting the learning process is to ensure that animals consuming sublethal doses of poisons on first contact with a bait will return for further feeding.
- One way of increasing the efficacy of a baiting programme is to control the consumption of bait by targeted animals so that an effective dose of active substance, or lethal dose of toxin, is more likely to be delivered on first contact. Focussing on consumption of baits, animals which sample unknown foodstuffs may not ingest sufficient toxins (or other active substance) at a first sampling for it to be effective, even with known foodstuffs this may be the case. Incorporating high levels of active substances, including toxins, into the bait so that the first sampling is more effective is one option for addressing this. However, this can be expensive and dangerous. Moreover, if the first sampling is not effective bait aversion may develop such that a particular bait will no longer be effective against the targeted animal. Instead, it will avoid the bait which it associates with illness or discomfort or other adverse effects.
- a further problem with control of some animals is the low density of animals per area of control region. This can make options for control such as bait stations or hunting difficult and economically unviable.
- the present invention provides a method of attracting a targeted animal species to a bait, the method comprising the use of an attractant substance, in or near the bait, which attractant substance includes at least one of the following: (i) one or more of dodecyl acetate or its chemical analogues; - J
- a bait which includes at least one of (i) to (iv) above.
- the present invention provides a bait adjuvant which includes at least one of (i) to (iv) above.
- the present invention provides a method of attracting an animal to a bait, the method comprising the inclusion in the bait of at least one of (i) to (iv) above.
- the present invention relates to the use of at least one of (i) to (iv) above to attract targeted animals to a bait or bait site.
- the mimetic substances are selected from the group including barbituates, alcohol based substances, and benzodiazepines, as well as similar mimetics that may influence GABA or related transmission.
- the present invention provides a method of controlling uptake of a bait by an animal, the method comprising the use of a bait adjuvant, in or near the bait, which comprises at least one of the following:
- neuropeptide Y or its analogues (a) one or more of neuropeptide Y or its analogues; (b) one or more neuropeptide Y antagonists;
- a bait which includes at least one of (a) to (j) above, with the proviso that the bait does not comprise (b), (f) or (h) above alone, or combinations thereof alone.
- a bait adjuvant which includes at least one of (a) to (j) above.
- a method for controlling uptake of a bait by an animal comprising providing in or near the bait at least one of (a) to (j) above.
- a method of controlling uptake of a bait by an animal comprising administering to said animal at least one of (a) to (j) above.
- a bait adjuvant for altering the stress response in an animal which bait includes at least one or more stress response altering substances.
- a method of altering the stress response in an animal comprising the use of one or more stress response altering substances in or near the animal's bait.
- a method of altering the stress response in an animal comprising the inclusion in the animal's bait of one or more corticosterones, or analogues or antagonists thereof.
- a method of altering the stress response in an animal comprising administering to said animal one or more stress response altering substances.
- the stress response altering substance comprises one or more corticosterones, or analogues or antagonists thereof.
- a further method of the invention provided is a method for re-attracting bait shy animals to bait, the method comprising employing a combination of two or more methods, baits or adjuvants of the invention referenced above.
- the present invention provides a complex bait or bait adjuvant comprising at least two compounds selected from the following groups A. B and C:
- the present invention provides a method of re-attracting bait shy animals to bait, the method comprising the use of a complex bait or adjuvant above.
- the present invention provides a bait or bait adjuvant comprising:
- A. (i) one or more of dodecyl acetate or its chemical analogues; (ii) one or more of oxytocin or its chemical analogues;
- the bait or adjuvant includes at least three compounds, with at least one compound being selected from each of groups A. B and C above.
- the baits and bait adjuvants of the invention preferably also include a lipid membrane transfer facilitator.
- the present invention also provides a method for increasing the speed of delivery of an active substance to one or more organs, of a targeted animal, the method comprising administering to said animal an active substance together with a lipid membrane transfer facilitator.
- the present invention is directed to the use of lipid membrane transfer facilitators to increase the speed of delivery of an active substance to one or more organs of a targeted animal.
- a preferred lipid membrane transfer facilitator is a pyrrolopyrimidine.
- the lipid membrane transfer facilitators may also be employed in known feedstuffs and baits.
- the target area is a vulnerable organ or the central nervous system.
- the brain is particularly suited for targeting.
- Brain target areas include the nucleus solitarius (NTS) and striatum.
- a method of the invention as defined above further comprising the use of a mechanism for increasing the speed of uptake of an active substance.
- the mechanism may be mechanical or chemical.
- the mechanism is preferably designed to stimulate the face or oral cavitv of an animal.
- a method of baiting an animal comprising administering to said animal an active substance formulated for administration to a targeted area.
- the target area is as defined above.
- an active substance formulation comprising an active substance and at least one of the following:
- GABA gamma-amino-4-butyric acid
- the active substance is a toxin.
- the present invention provides a toxin formulation comprising (i) to (iv) and optionally (v) above.
- a method of poisoning an animal comprising administering to said animal a toxin formulated to target the striatum and/or NTS brain areas of the animal.
- a method of effectuating a rapid death in an animal comprising administering to said animal a toxin formulated to target the stratum and/or NTS brain areas of the animal.
- the present invention provides a method lessening the symptoms of poisoning or severity of the symptoms, in an animal, the method comprising administering in addition to a toxin, an adjuvant or bait of the invention.
- the present invention provides a method of lessening the symptoms of poisoning or severity of the symptoms, in an animal, the method comprising the use of an adjuvant or bait of the invention near a bait or toxin but separate therefrom.
- compositions for lessening the symptoms or severity of the symptoms exhibited by a poisoned animal include at least one or more of the following:
- the invention further comprises a method for preventing or treating poisoning in an animal, the method comprising administering one or more antidotes which can prevent damages to other areas of the brain by their actions on pathways in the brain activated by toxins.
- a preferred anti-emetic is a serotonergic antagonist and a preferred anxiolytic is a cholecystokinin antagonist.
- the methods of the invention may be further enhanced by the use of a pre-baiting step which comprises administering to the targeted animal, baits free of an active substance to be administered later, but otherwise having the same attributes as the bait.
- a method of the invention which includes as a pre-step administering to a targeted animal species an active substance-free bait of the invention.
- the methods of the invention may also alternatively be enhanced or supplemented by the use of two or more, but preferably two, adjuvants or baits at the same time and at the same site.
- both a bait and an active substance-free bait of the invention are present.
- the bait is a bait of the invention.
- a method of the invention which further comprises the simultaneous use of a bait and an active substance-free bait at a bait site.
- the bait is a bait of the invention.
- the methods of the present invention may also be used in combination with existing bait aversion reversing techniques to re-attract and control bait shy animals.
- Figure 1 Demonstrates the attractant ability, in terms of visits to a source, of oxytocin and/or GABA and their effect in re-attracting bait shy animals to a bait-shy material. Data present as meant +S.E.M from repeat measure Anova. a: p ⁇ 0.01 (control); b: p ⁇ 0.01 (control)l c: p ⁇ 0.01 (bait shy); d: p ⁇ 0.05
- Fiaure 2 Illustrates attractant ability of dodecyl acetate (DA) on field rats with or without oxytocin and GABA in the field at two sites (S 1 and S2) before and after the development of bait shyness to the bait material.
- DA dodecyl acetate
- Figure 3 Demonstrates the ability of dodecyl acetate (da) in combination with oxytocin (o) to attract to a particular site in a two site choice procedure (site
- Readings represent day l(dl), day 2 (d2) and overall mean (4 days).
- Figure 4 Exhibits the effect of different bait additives on increasing consumption of a bait (expressed as a % of the normal feed level).
- NPY neuropeptide
- HTA serotonin antagonist
- CCKA cholecystokinin antagonist
- GLUTA glutamate antagonist
- CONT control substance
- Figure 5 Represents a similar experiment to that expressed in Figure 4 but for possums as a species. In addition the effects of modulating stress are shown through the use of a cortisol antagonist.
- Figure 7 Illustrates the effects of feed additives in curtailing consumption of a feed.
- CCK cholecystokinin
- Figure 8 Demonstrates the enhancement of toxic effect with the addition of a pyrrolopyrimidine (PP). Cumulative animal death was increased within 3 time intervals 6, 12, 24 hours after ingestion.
- PP pyrrolopyrimidine
- Figures 9 are flow diagrams illustrating a single and two step procedure for greater and 10: field kill effectiveness.
- Figure 11 Is a bar graph illustrating the effectiveness of glutamate/NOS antagonists in preventing 1080 toxin damage.
- Figure 12 Is a bar graph illustrating the effectiveness of GABA antagonists in preventing 1080 toxin damage.
- Figure 13 Is a bar graph illustrating the effectiveness of salicylate in preventing 1080 toxin damage.
- Figure 14 Is a bar graph illustrating the effectiveness of glutamate NOS antagonists and GABA agonists in preventing 1080 toxin damage.
- Figure 15 Changes in concentration ( ⁇ mol/1) GABA and glutamate in the somatosensory cortex following probe insertion (-2.5 h) and saline administrations (0 h). Similar changes where seen for the cerebellum and striatum. Data present as mean ⁇ S.E.M.
- Fieure 16 Changes in glutamate ( ⁇ mol/1) in different brain areas following oral administration of 1080 and saline (0 h). Data are mean ⁇ S.E.M.
- Figure 17 Changes in GABA ( ⁇ mol/1) in different brain areas following oral administration of 1080 and saline (0 h). Data are mean ⁇ S.E.M.
- Figure 18 Is modified Latin Square testing of the independent variables: the trial substances (one substance per feeder, two per trial). Shadowing indicates substance versus substance.
- Figure 19 Is a bar graph illustrating the effects of attractants and repellants on feed consumed. The feed consumed per day was calculated from total consumption in trial for that substance divided by days that substance was presented. Data presented as mean and S.E.M.
- Figure 20 Is a bar graph illustrating the effects of attractants and repellants on eating occurrences of substances. Total occurrences for each substance in trial for that substance divided by days that substance was presented are given. Data presented as mean and S.E.M.
- Figure 21 Is a bar graph illustrating the effects of attractants and repellants on animals numbers per day. Total numbers of animals in a 10 metre radius per day are shown. Individuals were not identified so may be represented more than once. Data presented as mean and S.E.M.
- Figure 22 Is a diagram depicting the layout of deer study site.
- Figure 23 Is a bar graph showing hay consumed from feeders associated with a particular attractant or repellant compound. Errors are S.E.Ms.
- Figure 24 Is a bar graph showing number of occasions a deer appeared to feed from a feeder associated with a particular compound. Errors are S.E.Ms.
- Figure 25 Is a bar graph showing the number of occasions when a deer approached a feeder associated with a particular compound. Errors are S.E.Ms.
- Figure 26 Is a bar graph showing ten minute focal scan results : Number of individuals standing within 10 m of a feeder associated with a particular compound.
- the present invention relates generally to methods for increasing the efficacy and acceptability of baits for use in biological pest control.
- Target biological pests include marsupials, birds, mammals, insects, arthropods, amphibians, and reptiles.
- the term "animal" is used generically to encompass all such pests.
- particular targets include rabbits, hares, possums, mice, and rats.
- a particular target marsupial is possums.
- any animal baiting campaign depends for its effectiveness upon targeted animals consuming an effective dose of an active substance, or a lethal dose of toxin in particular. To achieve this result it is necessary to both attract targeted animals to a bait and to ensure that they consume an effective or lethal dose of active substance or toxin as appropriate.
- attractant substances to draw targeted animals to a bait is known in the art. For example, the use of compounds such as colour lures, pheromones, sweeteners, and aromatic agents has been proposed.
- Dodecyl acetate has proved particularly useful. It appears to act as a long distance attractant and has been shown to act as such for elephants [36]. Combinations of two or more attractant substances are specifically contemplated.
- a preferred combination of attractant substances comprises GABA and oxytocin, and optionally dodecyl acetate.
- Butyric acid groups have been purported to have attractant properties [38]. Oxytocin appears to have a social facilitating effect causing animals to group together. GABA appears to have a similar effect.
- oxytocin and dodecyl acetate are potent attractants in rabbits, rats and possumes in up to a 2 km attractant range ([35] incorporated herein by reference).
- the applicants have devised a method for attracting a targeted animal species to bait, the method comprising the use of an attractant substance, in or near the bait, which attractant substance includes at least one of the attractant substances set out above.
- baits which include at least one of the attractant substances set out above.
- present invention provides a bait adjuvant which includes at least one of the attractant substances set out above.
- mimetic substance is used generally herein to refer to those substances which have the same or substantially the same activity and effect as those substances identified as (i)-(iii) above. These mimetic substances may comprise substances which stimulate the same pathways within the animal's physiology (particularly neural pathways), or within the social communication network of the animal species, as (i)-(iii).
- the mimetic substances are selected from the group including barbituates, alcohol based substances and benzodiazepines (such as benzodiazepan), as well as similar mimetics that may influence GABA or related transmission.
- adjuvant is used herein to refer to a compound per se or a composition formulated for use in or near bait.
- the adjuvant may increase the effectiveness, assist in attracting animals to, or assist in increasing the uptake or consumption of, the bait.
- adjuvants may include substances which alter the lifetime of the attractants, their volatility, distance over which the attractant is effective, and availability to the senses of smell or taste of a targeted animal species.
- Slow release formulations are also contemplated. This may be achieved using chemical agents or mechanical devices such as are known in the art. For example, a slow releasing dialysate type mechanism.
- Adjuvants can be similarly used with respect to the uptake and consumption control compositions.
- analogue used herein includes acceptable salts, derivatives, and isomers of the chemical compound in question as may be known in the art.
- bait refers broadly to any material which is suitable for use in making an active substance available in the environment of a targeted pest species, or for administration to a targeted pest species.
- the bait is an edible material or feedstuff.
- any suitable delivery method known in the art may be employed. This may comprise self-administration or administration by mechanical devices or humans. Some methods of administration contemplated include oral, topical, nasal and parenteral methods of administration, but are not limited thereto. It is presently considered that oral ingestion by an animal is the most feasible and effective manner of administering bait and adjuvants of the invention to a targeted animal species.
- baits include for example, vegetable, meats and commercial pastes and feedstuffs such as hay, meal and silage, but are not limited thereto.
- the bait selected will be a bait particularly attractive for consumption by the targeted animal.
- this may comprise injection via a mechanism in which a needle or sharp object at a bait station can prick the animal and introduce an effective dose of the active substance or toxin.
- Topical administration may comprise self-application via scratching or rubbing of the animal against a mechanical surface to which the compound is applied.
- sprays or vapours which are topically administered or inhaled are further possibilities.
- the optimal method of administration can be selected depending on the toxin to be administered and the bait to which it is to be incorporated.
- the levels of the active substances and toxins present in the adjuvants or baits will vary according to the bait composition or feedstuff to be consumed by the targeted animal species.
- An active substance or toxin may comprise anywhere from 0.0001 to 99.99% of a composition. Preferred ranges are from 0.1 to 50% and more preferably 1 to 20%. Where small amounts are being consumed or otherwise administered, then a higher concentration of active substance will be required. Where smaller baits are to be consumed, an increase in the concentration of the active substance is feasible.
- an effective amount of a compound is expected to vary from about 0.01 milligrams per kilogram of body weight to about 1000 mg/kg.
- Preferred amounts are expected to vary from 0.5 to 100 mg/kg, and preferably 1 mg to 50 mg/kg. Appropriate amounts can be readily calculated by a skilled worker.
- bait compositions known in the art may be employed, for example, baits with a graduated concentration of active ingredient there through rather than uniformly dispersed therein. Baits or feedstuffs with active agents sprayed there over is one method of achieving this result.
- Active substances which may be targeted to a pest species include toxins, contraceptives, vaccines, repellants and anti-infective agents, but are not limited thereto.
- the active substance is a toxin.
- Toxins suitable for use herein include sodium fluoroacetate (1080), warfarin, arsenic, cyanide, strychnine, brodificoum, cholecalciferol and similar new generation anticoagulants and coagulants, but are not limited thereto. Any suitable toxins known in the art may be employed.
- compositions proposed above various other substances may be included in the bait compositions and adjuvants, including other attractants, flavour enhancers, substances increasing palatability of the bait, masking agents which can cover any unpleasant taste or smells associated with the bait compositions, repellants directed against non-targeted animal species, preservatives, lubricants, antioxidants, buffers and the like.
- acceptable carriers and diluents in the baits and adjuvants is also contemplated.
- a presently preferred attractant is decanolactone or its analogues, or functional equivalent.
- decanolactone has variable attractant properties on its own, it surprisingly potentiates the effects of other attractants particularly DA and/or oxytocin-GAGA above what would be expected for the attractants alone. Accordingly, in one aspect decanolactone is also used in the baits, adjuvants and methods of the invention.
- the baits may also be formulated to include compositions which have a calming effect on the animal.
- Some appropriate dietary compositions are contemplated in NZ 329084 filed 29 October 1997, and incorporated herein by reference and annexed.
- bait compositions there are substances which can inhibit the effectiveness of the active ingredients of the compositions of the present invention. This may be by reacting with or competing with the active ingredients, thereby reducing their effectiveness.
- substances compatible with bait compositions can be determined by review of manufacture data sheets from specific active ingredients to determine which substances are to be avoided in bait compositions and adjuvants of the invention.
- bait site is used herein to refer broadly to anywhere bait is located for access by a targeted animal species. This may include man-made bait stations.
- a significant factor in the efficacy of baiting campaigns is the level of uptake of an active substance by a targeted pest.
- the following discussion focuses on consumption of toxins but is not limited thereto.
- one or more serotonin releasing factors may be used in controlling uptake of a bait by an animal.
- controlling uptake is used herein to refer to either increasing or decreasing uptake of the bait by the animal to ensure that an effective dose of active substance is delivered.
- Uptake generally comprises consumption but as discussed above is not limited thereto.
- the substances identified above may be used to increase or decrease consumption as required. Increasing consumption may be required to ensure that a full dose of active substance is consumed. Decreasing consumption may be required where animals consume more active substance than is needed. Decreasing consumption in this case reduces wastage and in long life field delivery setups may extend the unattended field life.
- the present invention provides a method of controlling uptake of a bait by an animal, the method comprising the use of a bait adjuvant in or near the bait, which adjuvant comprises at least one of the following: (a) one or more of neuropeptide Y or its analogues; (b) one or more neuropeptide Y antagonists;
- a bait which includes at least one of the group of compounds (a)-(j) set out above.
- a bait adjuvant which includes at least one of (a)-(j) set out above.
- the bait will not comprise (b), (f), (h) alone or combinations thereof alone.
- a method of controlling uptake of a bait by a targeted animal comprising the inclusion in the bait of at least one of (a)-(j) above.
- the compounds (a)-(j) identified above have been found to be particularly effective in increasing consumption of bait.
- the bait adjuvant need not be included in the bait but plays an effective role if placed in proximity to the bait, for example, at the same bait site.
- the degree of proximity of the bait to the bait adjuvant to be effective when not incorporated in the bait will depend on the animal being targeted, the bait being used, and the type and concentration of active substances therein and in the adjuvant. Optimum levels of proximity can be readily determined by skilled workers in this field.
- neuropeptide Y compounds the preferred peptide is [Leu 31 , Pro 34 ] Neuropeptide Y.
- Preferred neuropeptide Y antagonists include [D-Thr 32 ] neuropeptide Y, Fragments 18-36 neuropeptide Y, and Methyl-Tyr neuropeptide Y, but are not limited thereto.
- Cholecystokinin is a recognised gastrin releasing peptide.
- a preferred cholecystokinin is CCK-8.
- Cholecystokinin antagonists preferred for use in the invention include proglumide, proglumide sodium salt. N-methyl-D-glucamine salt. PD 142.898, PD 135.138. benzotript. RB21 1. CI988. L365260 Lorglumide sodium salt.
- Serotonin is a well known neurotransmitter.
- Preferred antagonists include ketanserin. cinanserin. MDL-72222, LY-278, 584, maleate. metergoline and methysergide maleate.
- re-uptake inhibiting factors examples include fluoxetine, fluvoxamine and paroxetine.
- Serotonin releasing factors include fenfluramines and amphetamines such as 4- methylthioamphetamine.
- Leptin is the protein encoded by the obese (ob) gene and acts on the central nervous system. Any known leptin peptides (e.g. Tyr-leptin) and antagonists may be used herein.
- the levels of compounds (a) to (j) for use in the invention may be varied in a similar manner as for the active substance according to size, age, health, etc. of the animal population.
- An effective amount of a compound is expected to vary from about 0.01 milligrams per kilogram of body weight to about 1000 mg/kg.
- Preferred amounts are expected to vary from 0.5 to 100 mg/kg, and preferably 1 mg to 50 mg/kg.
- a further important element in the effectiveness of an animal baiting campaign is being able to alter the stress response in an animal.
- the present invention provides a bait adjuvant for altering the stress response in an animal which bait includes one or more corticosterones. or analogues, or antagonists thereof.
- corticosterone antagonist contemplated for use include RU38486 (mifepristone) and RU 28318.
- Levels of corticosterone antagonist used in the invention vary as for (a) to (j) above.
- the present invention provides a method for altering the stress response in an animal, said method comprising the use of one or more stress response altering substances in or near the animal bait.
- a method of altering the stress response in an animal comprising the inclusion in the animal bait of one or more stress response altering substances.
- the present invention also provides a method of altering the stress response in an animal, said method comprising administering to said animal one or more stress response altering substances.
- the stress response altering substances are selected from corticosterone compounds, analogues or antagonists identified above.
- the invention provides a method for re-attracting bait shy animals to bait, the method comprising employing a combination of two or more methods, baits or adjuvants of the invention as referenced above.
- the stress response altering bait adjuvant identified above can be used in re- attracting bait shy animals to bait.
- the present invention provides a complex bait or adjuvant comprising at least two compounds selected from the following groups A, B and C:
- GABA gamma-amino-4-butyric acid
- the present invention provides a method of reattracting bait-shy animals to a bait, the method comprising administering at least two compounds of A, B and C as above.
- the baits or adjuvant includes at least three compounds, with at least one compound being selected from each of groups A, B and C.
- Another important element in the effectiveness of animal treatment campaigns is the speed at which compositions act on the targeted animal species.
- animal welfare concerns dictate that the time between consumption of a toxin and death should be as short as possible and as painless as possible. At least, efforts should be made to minimise animal suffering.
- lipid membrane transfer facilitator refers to a compound facilitating transfer of active substances across lipid membranes. Their general effect is to facilitate transfer of active substances into target organs or the CNS, and desirably at higher concentrations than would otherwise often be possible, and typically within a shorter time span.
- the substance to be administered is a bait toxin and the main target organ is the brain.
- the present invention provides baits and adjuvants, including those of the invention, which further comprise a lipid membrane transfer facilitator.
- lipid membrane transfer facilitators to speed the delivery of an active substance to target organs of an animal is also contemplated.
- a method for increasing the speed of delivery of an active substance to one or more organs of a targeted animal comprising administering to said animal an active substance together with a lipid membrane transfer facilitator.
- facilitators may also be included in known baits to enhance transfer of active substances to targeted organs.
- the preferred lipid transfer membrane facilitators of the invention comprise lipid penetrating antioxidant compounds such as pyrrolopyrimidines and analogues thereof but are not limited thereto.
- a preferred pyrrolopyrimidine is U-101033E. Examples of pyrrolopyrimidines useful in the present invention are given in Hall Ed. et al., 1995 Ada NeuroChir, 66: 107-113, and Andreous P et al., 1997 J. Neuro Science Res., 47: 650-654.
- lipid transfer membrane facilitators may be provided as adjuvants, that is, in the form of the compound per se or formulated into baits. In such cases, the compounds may be conjugated to components of these baits. Combinations of selected lipid transfer membrane facilitators, as well as combinations of conjugated forms, are also contemplated for use.
- the efficacy of administration of an active substance to an animal can be increased by targeting the active substance to a vulnerable area in the animal.
- Vulnerable target areas include organs and the Central Nervous System (CNS).
- the brain is a particularly suitable tar ⁇ et.
- NTS nucleus tractus solitarius
- striatum are areas of the brain which show particular vulnerability to toxin damage contributing to the lethal effects of toxins. Uptake of toxins into the NTS in particular can be achieved through activating or stimulating the trigeminal system.
- Other methods for increasing the speed of toxin uptake into vulnerable target organs, particularly the brain therefore also include the use of stimulant mechanisms, more particularly those aimed at stimulating the trigeminal system.
- These mechanisms may be mechanical or chemical in nature. Examples of ways in which the mechanisms may be used, is in the stimulation of the face or oral cavity of an animal. The stimulation may consist of, for example, irritation or cooling. These actions activate the trigeminal system facilitating uptake of substances in the NTS brain area.
- Suitable mechanical stimulant devices include sprays, fans, brushes and the like.
- a spray associated device that delivers a cold spray onto the face of an animal is desirable.
- Chemical irritants and coolants are also contemplated for use.
- an active substance formulation comprising an active substance and at least one of the following: (i) one or more of dodecyl acetate or its chemical analogues;
- a combination of at least one of each of (i)-(iv) is preferred.
- Also forming an aspect of the present invention is a bait including such an active substance formulation.
- the present invention provides a method of poisoning an animal, the method comprising administering to said animal a toxin formulated to target the stratum and/or NTS brain areas of a targeted animal species.
- a toxin formulated to target the striatum and/or NTS brain areas of a targeted animal species.
- one or more antidotes which can prevent damage by their actions on pathways in the brain activated by toxins. Their use in the event of accidental poisoning is particularly contemplated.
- the present invention provides a method of preventing or treating poisoning in an animal, the method comprising administering one or more antidotes which can prevent damage to other areas of the brain by their actions on pathways in the brain activated by toxins.
- the antidotes may be used to reduce specific tissue damage and the attendant side effects arising therefrom. Suitable antidotes are given below. Administration of two or more antidotes may be sequential or simultaneous.
- Antidotes contemplated for use in the present invention include:
- antidotes of types (I) to (VI) such as are known in the art may be used.
- antagonists and anti-inflammatory agents are dextromethorphan, phaclofen, bicuculline, D-AP5, APH, APV, kynurenic acid, CNQX disodium, L-N 5 , N G - Monomethyl-L-arginine acetate, L-NOARG and the like.
- opioid agonists examples include DAMAGO (D-Ala 2 , N-Me Phe 4 Gly-01 5 ]-enkephalin) and GR 89696 (4-[(3,4- dichlorophenyl)acetyl]-3-(l-pyrrolidinyl methyl)- 1-piperazine carboxyl acid methyl ester fumurate).
- steroidal hormone mimics examples include ⁇ -estradiol and progesterone sulphate. Appropriate levels of antidote may be selected by a skilled worker.
- Poisoning results in a raft of noxious sensations and perceptions in the poisoned animal.
- Symptoms include hypersensitivity to light and/or sound, convulsions, ataxia (meaning herein a maintained tilting of the head or body or a tendency to fall over), increased water intake, drop in feed intake, balling (lying in a ball while awake), pacing, grooming or scratching of the abdomen. All of these symptoms may be reduced by the administration of the adjuvant or bait of the invention.
- the present invention provides a method of lessening the 13 symptoms of poisoning or the severity of the symptoms in an animal, the method comprising administering in addition to a toxin, an adjuvant or bait of the invention.
- the bait or adjuvant of the invention includes one or more anxiolytic and/or antiemetics.
- Any suitable anxiolytic and antiemetic compounds known in the art may be used.
- Any of the serotonergic antagonists and cholecystokinin antagonists set out above may be used.
- the methods of the invention may be further enhanced by the use of a pre-baiting step which comprises administering to a targeted animal species an active substance-free baits otherwise having the same attributes as baits to be used in later baiting programmes.
- a method of the invention which method includes as a pre-step administering to a targeted animal species an active substance-free bait.
- Figure 9 provides a flow diagram of the methods with reference to the consumption of toxins.
- the methods of the invention may alternatively be enhanced or supplemented by the use of two or more, but preferably two, adjuvants or baits at the same time, at the same site.
- one bait is a bait of the invention, or as is otherwise known in the art, and the other active substance-free bait or adjuvant of the invention corresponding thereto.
- the present invention provides a method of the invention which further comprises the simultaneous use of a bait and an active substance-free form of that bait at a bait site.
- the active substance in this method is a toxin.
- Figure 10 provides a flow diagram of the methods with reference to the consumption of toxins.
- toxin-free baits are made available to the target animals.
- the baits employed are the attractant baits of the invention and/or baits formulated to control uptake according to the invention. These baits should have the same attributes as the baits to be provided later.
- the rationale is that the animals will consume these baits and not develop an aversion. If the baits prove palatable and rewarding, this will increase the animals consumption and future exposure. While not being bound by this, it is believed that the use of methods of the invention and related baits to control consumption will cause the animals to consume greater levels of these baits on initial consumption, thereby further increasing the animals classification of the bait compositions as safe and rewarding whilst the use of the attractant methods and baits will cause a greater number of animals to be exposed to the baits. All those baits, including the toxins, are then made available. The animals should recognise the baits as preferred and therefore consume large volumes of the bait increasing chances of receiving a lethal dose of poison.
- baits at a site wherein both baits are baits formulated to control consumption according to the invention are preferred to allow quick classification of the bait as being safe, while baits additionally comprising the attractant adjuvant of the invention may be used to attract more animals.
- One bait composition would then be altered to include a toxin or replaced with a toxin- containing bait of the invention. The other would not be changed. If the targeted animal species had other mechanisms that made them stop eating the toxin-containing baits then they may be more likely to continue eating the toxin-free bait compositions. This would increase the probability that they would consume enough of the control consumption baits including more of the toxin-containing bait.
- the benefits of the two bait system with only one containing the toxin is the probability of the other "unknown" mechanisms interfering with consumption to an effect level, could be avoided. If a sublethal dose is consumed, the use of the consumption controlling composition should prevent subsequent aversion developing, and the animal should consume the baits again on further exposure and maintain a susceptibility to poisoning.
- NPY neuropeptide Y
- 5HTA a serotonin antagonist - ketanserin
- CCKA a cholecystokinin antagonist
- GLUTA glutamate antagonist (dextromethorphan).
- NPY neuropeptide Y
- 5HTA a serotonin antagonist - ketanserin
- CCKA a cholecystokinin antagonist
- GLUTA glutamate antagonist (dextromethorphan).
- mice Ten days prior to the start of experimentation animals were anaesthetised using a mixture of zolazepam/tiletamine hydrochloride (Zoletil, Techver Lab. New Zealand) and 2% xylazine (Rompun. Bayer, Germany) both administered intramuscularly at 0.1 mg/kg liveweight.
- Antibiotics (Depomycin, Mycofarin, Boxmeer. Holland) were administered intramuscularly (0.4 ml) as a prophylactic measure 6 h prior to surgery and on the two days immediately postsurgery.
- the head was shaved, swabbed with 70% ethanol and covered with an iodinated sterile drape.
- An incision was made 1 to 2 cm in length, through the skin and scalp and skull exposed and cleaned.
- the bone suture landmarks, bregma and lambda were used to stereotaxically identify: somatosensory cortex, striatum, purkinje cell layer of the cerebellum, and the nucleus tractus solitarius.
- sterile guide cannulae 25 gauge polypropylene catheter
- Prophylactic postsurgical analgesia lOOmg soluble aspirin (Solptin, Reckitt and Colman, New Zealand), was administered orally twice daily for three days after surgery.
- microdialysis probes ME.C-P2, Applied Neuroscience. London, NW1 6DT, UK
- the microdialysis probes were perfused with an artificial cerebrospinal fluid (ACSF) mixture at a rate or 2 ⁇ l/min driven by a syringe pump (MS16A, Graseby Medical, UK) as has previously been described [13], [14]. Collections were made on a 5 min sample basis (lO ⁇ l per sample). Samples were analysed off-line using HPLC techniques as previously described [13] . [14], [17].
- ACSF cerebrospinal fluid
- the microdialysis probes contained a chlorided silver wire and electroencephalograms (EEG) of the animal were derived from the potential between this and an Ag/AgCl reference electrode placed onto the animal's skull.
- EEG chlorided silver wire and electroencephalograms
- the potential between the electrode in the probe and the reference was amplified using high-impedance pre-amplifier (NL 102G, Neurolog System. Digitimer, Ltd. Welwyn Garden City, UK) and the AC component in the 1-30 Hz window amplified to provide EEG.
- Linear spectra of consecutive EEG data sections (4s) were computed using Fast Fourier transformation and for each 4s epoch the average amplitude of the EEG linear spectrum computed and displayed.
- microdialysis probes also contained an associated cannula that allowed direct introduction of pharmacological agents into the neural area from which sampling was made. All tubing and wires were suspended from the top of the cage to the animal's head and animals were tethered allowing them relatively free movement within a cage while measurements were made.
- Samples were collected for 2.5h and then animals were given either two oral administrations each of 1 ml 0.9% sterile saline via a syringe (40 animals) or a lO ⁇ l perfusion via the cannula associated with the microdialysis probe (20 animals). Administrations were given over a 10 min period. Measurements were then continued for another 18 hours. At the end of that time, microdialysis probes were removed and obturators replaced.
- the experimental sequence was repeated 3 d later with all animals receiving an oral administration of 1 ml sterile saline containing 3.5 mg/kg liveweight 1080.
- 20 animals received a further oral administration of 1 ml sterile saline alone and 20 animals this containing one of:
- GABA receptor agonists - 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP HCC) and allopregnanolone both at lOmg/kg liveweight.
- the remaining 20 animals received, in addition to the 1080, a microdialysis associated cannula perfusion of lO ⁇ l (over 10 min) sterile saline containing one of: I. glutamate receptor and nitric oxide synthase antagonists as above at 5 ⁇ g each.
- GABA receptor agonist as above at 10 ⁇ g each.
- EEG EEG was monitored continuously and any incidence of ataxia, wet dog shakes, convulsive-like activity including clonic or tonic-like movements recorded. Shallowed or laboured breathing were also recorded. With severe respiratory depression, accompanied by subjective unconsciousness, ausculation was used to determine heart beat rate.
- Microdialysis probes showed in vitro recoveries of between 20 and 30%, with individual probes varying less than 10%. Stability was maintained from before to after experimentation and postmortem histology indicated all probes to be within 1 mm of their target areas.
- Probe insertion disrupts neural function slightly, and a transient increase in extracellular neurotransmitters accompanied by DC and potassium ion shifts have been previously reported, [18], [19]. Usually these appear to settle back to basal levels within 15-30 mins, and comparative observations were obtained herein. Glutamate is recognised as a neurotransmitter involved in alert behaviours [25] and its increase in certain brain areas with the handling associated with transient increased in both glutamate and GABA that returned to baselines within 5-10 mins. These transient increases may result from a similar type of neural area disruption as seen with initial probe insertion. Probe insertion and perfusions were not associated with any obvious changes in subjective behaviour nor in the EEG amplitude which remained between 10 and 30 ⁇ V for the duration of measurement.
- Table 2 Percentage of animals exhibiting neurological dysfunctions following oral administrations and time range at which these occurred (min) after administration
- Percentage of animals in each group is displayed as is the upper and lower range of time after oral administration at which symptoms were observed.
- Ataxia was defined by a maintained tilting of head or body or a tendency to fall over.
- a total of 60% of the animals in this group displayed one or more seizures and 80% of animals died within 18 h of 1080 administration. Although the dose used was less than LD80, animals were fasted prior to administration and this may have increased the fatality rate and reduced duration to time of death.
- GABA administration had no effect on either glutamate or GABA levels.
- administration into the somatosensory cortex reduced hyper-responsiveness to both light and sound and reduced incidence of cage pacing (p ⁇ 0.05).
- Administration into the striatum reduced convulsions, ataxia, and fatalities (p ⁇ 0.05) but had no effect upon light/sound hyper-responsiveness not cage pacing activity.
- Administration into NTS also reduced convulsions, reduced respiratory depression, and fatalities (p ⁇ 0.05).
- Administration into the cerebellum had no obvious effects.
- GABA administration gave similar results although there was also an accompanying reduction in glutamate levels. GABA alone did not appear as effective at preventing fatalities or respiratory depression as glutamate/NOS antagonism.
- glutamate/NOS antagonists and GABA were chosen because of their proven reduction of hypoxic-ischemic type damage in other models [7], [8], [20],[21], [22], [23]. This study strongly suggests that glutamate excess may underlie many of the neurological dysfunctions associated with 1080 poisoning. It may also be a contributor to ultimate death. Triggering of NO via glutamate activation may also be a potential contributor although in this study effects of glutamate were not separated out from those of NO. Both glutamate and NO appear to contribute to convulsions as these are reduced by their antagonism.
- GABA In cyanide toxicity, both glutamate and NO (via peroxidation) contribute to neural damage and convulsive states [4], and this may be a common pathway for many energy deprivational insults that affect the CNS. Release of GABA appears to slightly lag in time glutamate and may be an attempt to control both glutamate levels and ensuing convulsive states. Potentiation of GABA, via agonists, not only reduced convulsions but also amount of glutamate released. A CNS area-time, after ingestion, relationship was seen that correlated with observed neurological behaviour. Glutamate in the somatosensory cortex was associated with hyper-responsiveness to both light and sound. This hyper-responsiveness was reduced by glutamate antagonists suggesting causal involvement of glutamate.
- Glutamate changes in both the striatum and cerebellum correlated in time with both observations of convulsions and ataxia.
- Glutamate antagonism in the striatum reduced incidence of both of these and of fatalities while in the cerebellum it appeared to have no effect.
- Changes in the cerebellum, in glutamate may be acting on receptors unaffected by the glutamate antagonists although this seems slightly unlikely as a broad receptor spectrum coverage was assured by the antagonist selection.
- glutamate change may only represent a marker of response, rather than effect, in the cerebellum. This does not belie a role of the cerebellum in neurological dysfunction but suggests this is not due to excess glutamate.
- Sodium salicylate was efficacious at preventing death when administered into the NTS, although had little effect in other areas. While glutamate contributes to neurodegeneration so does accompanying inflammation. Salicylate appears protective to this later mechanism [20]. It may be that part of the final pathway to death lies in inflammation of the NTS neurones and salicylate acts to reduce this. As there was no lasting neurological dysfunction in surviving animals, other areas of the brain affected by 1080 may not have experienced any substantial degree of inflammation. This would be consistent with a lack of apparent effect of salicylate in these other areas. Why the NTS should be more susceptible remains unknown but offers an avenue for exploration of toxin effect. Glutamate and GABA release may be a generalised response to 1080 toxicity.
- glutamate does appear to have a time separation in terms of appearance in different areas, and at least in some areas its manipulation can influence specific neurological manifestation. Its appearance may relate to spread of 1080 through the CNS or site specific vulnerability. Manipulation of both glutamate receptor activation and possible CNS area inflammation at the central level reduced some of the toxin effects of 1080 but oral administration was less effective. This may relate to the titre of drug reaching specific CNS areas in the appropriate window of time. Measuring specific neurotransmitter changes in conscious animals and correlating these, via pharmacological manipulation, with neurological behaviour changes offers and approach to understanding toxic effects on the central nervous system.
- 1080 initiates excitotoxin-like reactions in a number of CNS areas that correlate with its neurological manifestations. This provides a platform for constructing a neural basis for understanding 1080 toxicity. In addition, neuronal inflammation appears contributive to final death following 1080 ingestion.
- Rats (20 males, body weights 300-400 g) were housed in separate cages and fed a standard cereal pellet mix (Diet 86, Sharpes Grain and Seeds Limited, Lower Hutt, NZ) at 60 g per day and 250 ml of water. Consumptions were recorded every 24 h. Animals were subject to a constant 21 °C environment and a 12 h: 12 h light/dark cycle. Fresh feed and water were provided at the start of the dark cycle, and during this cycle the room was lightly lit via two desk lamps with 15 W bulbs (to allow behavioural observation). Following 14 d of this the animals were divided into two groups of 10.
- Diet 86 Sharpes Grain and Seeds Limited, Lower Hutt, NZ
- Data are presented as mean ⁇ SD. Data were summed for all animals w t n the treatment group within the defined time irrespective of administration sequence as analysis showed this to have no significant effects.
- Hypersensitivity to sound or light was defined by the animal actively moving away or cringing from the source or showing a jumping startle-like response. Animals were awake at time of testing and experimenter's hand lowered slowing close to the animal before turning on the torch or clicking fingers.
- Cage pacing was defined by repetitive movement (more than 3 times in a sequence) up and down the cage during a single observation not exceeding 2 minutes.
- Convulsive-like behaviour was defined subjectively by the presence of either tonic or clonic-like movements and apparent loss of consciousness. Awakeness while lying in a ball was judged by eyes being opened. Other behaviours are self descriptive.
- mice received either: (i) 1 ml of 0.9% saline containing 5mg/kg liveweight of l-methyl-N-(8- methyl-8-azabicyclo [3.2.1]-oct--3-yl)-lH-indazole-carboxamide maleate (LY-278,584), a specific 5-HT 3 antagonist or (ii) 1 ml of 0.9% saline containing 2 mg/kg liveweight of PD 135, 158 N-methyl ' -D-glucamine, a specific cholecystokinin (B subtype) antagonist.
- Cholescystokinin antagonists co-administered with 1080 reduced significantly (pO.Ol) the amount of cage pacing and (p ⁇ 0.05) grooming and scratching of abdomen (Table 4)
- Hypersensitivity to sound or light was defined by the animal actively moving away or cringing from the source or showing a jumping startle-like response. Animals were awake at time of testing and experimenter's hand lowered slowing close to the animal before turning on the torch or clicking fingers.
- Cage pacing was defined by repetitive movement (more than 3 times in a sequence) up and down the cage during a single observation not exceeding 2 minutes.
- Convulsive-like behaviour was defined subjectively by the presence of either tonic or clonic-like movements and apparent loss of consciousness. Awakeness while lying in a ball was judged by eyes being opened. Other behaviours are self descriptive.
- the antagonist chosen has reported properties of both anxiolysis and mild gastric relief. Interestingly, hypersensitivity to both light and sound were not reduced by cholecystokinin treatment. This suggests they may not be a product of generalised anxiety. Two animals, one in each antagonist group, demonstrated convulsions and were euthanised. Although this is a significant reduction, compared to the non-antagonist groups, it is likely to reflect statistical variance around the 1080 dose effect rather than on treatment.
- a flock of 60 Angora goats were used for the duration of the trial.
- the animals were kept in one of three paddocks in a grazing rotation schedule.
- the paddocks consisted of: 4.5, 3.5 and 3 acres of open land, and water was available ad libitum. Animals were individually tagged. Trials were undertaken in the months of September, November and December. Animals were individually weighed each week bar one (where normal farm practice prevented this). Procedures
- feeders Two feeders were placed in the observation paddock. These feeders were lm x lm in size and contained lucerne chafe as the feed source. Associated with each feeder was a small container (adapted from a plastic jar) containing a Whatman 70 mm filter paper to which approximately 2 ml of the test attractant substance was added. This was topped up with 0.5 ml daily.
- New containers were used for each compound and each week of trial and at all times during handling latex gloves were worn to avoid cross contamination.
- Feeders were positioned approximately 250m apart in a line and observers (one for each feeder) positioned 5- 10m away from each feeder (observable by the goats). The areas in which the feeders were positioned were chosen on the basis of previous work showing these areas were frequented regularly by the goats throughout the day.
- each feeder was filled with 2 buckets of chafe that was weighted. Observations were made between 0900 and 1 lOOh, 1300 and 1500h and 1600h to 1800h. At the end of each observation period the remaining chafe was weighed and removed. This was returned immediately prior to the next observation period. If the first allotment of food was consumed during the day, it was immediately replaced.
- a modified form of a Latin square design as depicted in Figure 18 was used to compare the various substances against others.
- the independent variables were thus the substances and the dependent variables: the observers, the feeders, the feed consumed, number of visitations, animals within a 10m radius of the feeders and the individual animals.
- MANOVA Multivariate analysis of variance
- the mixture of oxytocin-GABA and decanolactone had the greatest effect (p ⁇ 0.01) in increasing consumption, increasing animals visitation and increasing the number of animals in a 10m radius of feeders containing this substance compared to the control substance.
- Ox-GABA and DA were both attractant, however the individual animals 'apparently' attracted by them differed slightly.
- Ox-GABA also attracted heavier animals but lighter animals were also present. Subjectively these lighter animals did not appear to be aggressively displacedOx- GABA and particularly Ox-GABA plus Dec attracted the greatest number of animals. However, this was due to the presence of the lighter weight animals. With DA, or its combinations, a greater number of heavier weight animals were present compared to the absence of DA.
- Ox-GABA on the other hand appears linked to social calmness and facilitation of grouping. This could account for the greater mix of different weight animals and the apparent "subjective" lack of aggression as compared to the DA containing mixtures.
- Formaldehyde sulphate has been suggested, in other species to be a highly effective repellent. It followed a similar pattern in the goats with an equal reduction in both heavier and lighter weight animals.
- a third compound decanolactone has variable attractant properties on its own but does potentiate the effects of DA and/or oxytocin-GABA.
- the object of this experiment was to test the effects of two potential attractants, dodecyl acetate and oxytocin, and a potential repellent, formaldehyde sulphate, on farmed red deer (Cervus elaphus).
- FS Formaldehyde sulphate
- OX oxytocin
- DA dodecyl acetate
- control 5% ethanol in water
- Experimental compounds were presented by soaking a 2 ml aliquot into filter paper (Whatman 70 mm) and were associated with each feeder by placing them in a small plastic container (adapted from a GladeTM fragrance dispenser) situated in the centre of each feeder. Experimental compounds were replaced daily.
- Pairs of compounds were tested by placing one in feeder 1 and the other in feeder 2. After 2 days the compounds were swapped to the opposite feeder where they remained for a further 3 days. Potential attractants were tested against one another and against the control. The potential repellent was tested against the control only.
- Dopaminergic neurotoxicity of cyanide Neurochemical, histological and behavioural characterisation. Toxicol. Appl. Pharmacol. 126, 156-163. [30 Carella, F., Grassi, M.P., Savoiardo, M., Contri, P., Rapuzzi, B. and Mangoni,
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WO1995028081A1 (en) * | 1994-04-13 | 1995-10-26 | The Meat Industry Research Institute Of New Zealand Inc. | Addressing bait aversion by disrupting associative learning |
WO1997015296A1 (en) * | 1995-10-23 | 1997-05-01 | Theratech, Inc. | Buccal delivery of glucagon-like insulinotropic peptides |
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1999
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WO1995028081A1 (en) * | 1994-04-13 | 1995-10-26 | The Meat Industry Research Institute Of New Zealand Inc. | Addressing bait aversion by disrupting associative learning |
WO1997015296A1 (en) * | 1995-10-23 | 1997-05-01 | Theratech, Inc. | Buccal delivery of glucagon-like insulinotropic peptides |
Non-Patent Citations (4)
Title |
---|
CLIVE TOMLIN, (Editor), "The Pesticide Manual", 10th Edition, Published 1994, by BRITISH CROP PROTECTION COUNCIL and THE ROYAL SOCIETY OF CHEMISTRY, (United Kingdom), entries 161, 333, 639. * |
DERWENT ABSTRACT, Accession No. 1987-089888/13, Class B03, (B07); & JP 62039572 A (HISAMITSU PHARMACEUTICAL KK) 20 February 1987. * |
DERWENT WPAT, Online Abstract, Accession No. 1984-240059/39; & JP 59142264 A (NITTO ELECTRIC IND CO) 15 August 1984. * |
DERWENT WPAT, Online Abstract, Accession No. 1988-341480/48; & JP 63253001 A (NITTO ELECTRIC IND CO) 20 October 1988. * |
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