Conditioned Food Aversion Research Articles

Specific Disruption of Memory Reconsolidation of Conditioned Food Aversion in Snails by DNA Synthesis Inhibitors.

The involvement of DNA synthesis in the mechanisms of long-term memory reconsolidation in edible snails trained for conditioned food aversion was investigated. Administration of nucleoside analogs, such as 5-bromo-2'-deoxyuridine or 3'-azido-3'-deoxythymidine, which inhibit DNA synthesis, 1 h before or 1-3 h, but not 5 h after reminder with the conditioned stimulus led to memory impairment. One day after the inhibitor application and memory reactivation, a weakly expressed memory impairment (amnesia) was observed, which progressed over the next few days to the complete disappearance of behavioral memory expression. In snails with formed aversive memory for two food conditioned stimulus, a specific memory impairment was observed only for the stimulus that was paired with the presentation of an inhibitor during the reminder, while the memory for the other non-reactivated conditioned stimulus remained intact. It is suggested that DNA synthesis in the brain plays a specific role in the genetic mechanisms of reconsolidation and maintenance of long-term conditioned food aversion memory in snails.

Chemical characterization and response of house rats towards faecal odour of conspecifics

Repeated use of rodenticides for rodent pest management leads to the development of bait shyness and resistance in rodents. Therefore, using pheromones for rodent management could be a significant step forward. The present study was conducted to determine the response of house rats towards odour of faecal extracts of conspecifics of different age groups and sexes. Rats of different maturity groups and sexes were exposed to 20% faecal extract of mature and immature male and female rats. Results indicated that faecal extract of estrous stage mature females has a significant attractant/repellent effect on mature rats of opposite/same sex, respectively. Gas chromatography-linked mass spectrometry of the faecal extract of estrous female rats identified 62 compounds, of which 16 were already reported in other animals as pheromonal compounds and might be used in communication by house rats. In the future, these identified compounds can be used in a fixed proportion after testing their efficacy to develop a stable lureto increase the trappability and acceptability of antifertility agents and rodenticide-based baits for the management of house rats.

Reversal of Conditioned Food Aversion Using a Cognitive Intervention: A Sham-Controlled, Randomized, Parallel Study

Background: Aversive conditioning weakens the gratifying value of a comfort meal. The aim was to determine the effect of a cognitive intervention to reverse aversive conditioning and restore hedonic postprandial response. Methods: This was a randomized, sham-controlled, single-blind, parallel study that was conducted on 12 healthy women (n = 6 in each group). The reward value of a comfort meal was measured on different days: at initial exposure, after aversive conditioning (administration of the same meal with a masked fat overload on the previous day) and after a cognitive intervention (disclosing the aversive conditioning paradigm in the test group vs. no explanation in the control group). The primary outcome, digestive wellbeing, was determined using graded scales at regular intervals before and after ingestion. Results: At initial exposure, the comfort meal produced a rewarding experience that was impaired using aversive conditioning; upon re-exposure to the original meal, the cognitive intervention increased meal wanting and liking; improved digestive wellbeing and mood; tended to reduce postprandial satiety, bloating/fullness; and abolished discomfort/pain, thereby restoring the hedonic value of the comfort meal. By contrast, sham intervention had no effects, and the postprandial sensations remained like the responses to the offending meal. Conclusion: In this proof-of-concept study, we demonstrate that in healthy women, a mild, short-term acquired aversion to a comfort meal can be reversed using a cognitive intervention. ClinicalTrials.gov ID: NCT05897411.

THE CONTRIBUTION OF EPIGENETIC MECHANISMS TO THE FORMATION, MAINTENANCE AND RECONSOLIDATION OF THE LONG-TERM FOOD AVERSIVE MEMORY IN TERRESTRIAL SNAIL

This work was devoted to the analysis of the role of epigenetic mechanisms (histone acetylation, DNA methylation, histone serotonylation) in the formation, storage, and reconsolidation of long-term food aversive memory in the snail. In the first part of the work, we investigated the effect of systemic administration of sodium butyrate, an inhibitor of histone deacetylase, in a model of conditioned food aversion reflex of the snail. We have shown that the administration of sodium butyrate to animals with poor memory resulted in memory enhancement. Further, in experiments using the DNA methyltransferase blocker RG108, it was found that impaired DNA methylation impairs long-term food aversive memory in the snail. However, memory reactivation neutralizes the effect of inhibiting the activity of DNA methyltransferases. In the final section of the work, the hypothesis of the involvement of transglutaminase-mediated serotonylation in the processes of reconsolidation of food aversive memory in the snail was tested. Behavioral analysis showed that administration of the transglutaminase blocker monodansylcadaverine (hence, blockade of serotonylation) after a reminder disrupted the reconsolidation process and led to memory suppression/erasure.

Epigenetic Processes of DNA Methylation Are Selectively Involved in the Mechanisms of Retrograde and Anteograde Amnesia.

The participation of DNA methylation processes in the mechanisms of anterograde and retrograde amnesia caused by impaired reconsolidation of conditioned food aversion memory by NMDA glutamate receptor antagonists or serotonin receptor antagonists, respectively, were studied on grape snails. Anterograde amnesia was characterized by impaired formation of long-term memory during repeated learning. Administration of a DNA methyltransferase (DNMT) inhibitor to amnestic animals resulted in accelerated formation of long-term memory during 1 day of repetitive training vs 3 days during initial training. In serotonin-dependent retrograde amnesia, repeated learning without DNMT inhibitor administration or after inhibitor injections led to the formation of long-term memory. The dynamics of memory formation was similar in both cases and did not differ from that during the initial training: the memory was formed within 3 days of training. Thus, epigenetic processes of DNA methylation are selectively involved in the mechanisms of anterograde amnesia, but do not participate in the mechanisms of retrograde amnesia.

Effects of interval between CS and US in food aversion conditioning in Japanese fire-bellied newts

Effects of interval between CS and US in food aversion conditioning in Japanese fire-bellied newts

Comparative Study of the Effect of a DNA Methyltransferase Inhibitor and a Histone Deacetylase Inhibitor on Memory Formation Processes in Anterograde Amnesia.

The participation of DNA methylation and histone acetylation in the mechanisms of anterograde amnesia and memory recovery was studied on grape snails trained in conditioned food aversion. Anterograde amnesia developed 10 days after memory reconsolidation impairment with an NMDA glutamate receptor antagonist and was characterized by long-term memory formation impairment upon repeated training. DNA methyltransferase inhibitor injections to snails 1 h before repeated training, as well as 15 min or 4 h after repeated training, caused rapid formation of memory that persisted for at least 10 days. Injections of histone deacetylase inhibitor before repeated training also induced the formation of a stable long-term memory. However, administration of histone deacetylase inhibitor 15 min after repeated training initiated a temporary memory recovery. Injections of the inhibitor 4 h after repeated training were ineffective. These results indicate that histone-dependent chromatin remodeling and DNA methylation are selectively involved in the mechanisms of anterograde amnesia and memory recovery.

Protecting prey by deceiving predators: A field experiment testing chemical camouflage and conditioned food aversion

Complicated conservation problems may arise if predator numbers increase beyond their natural boundaries due to anthropogenic influence. For example, dramatic declines in ground-nesting birds are linked to increased nest predation by alien or human-subsidized mammals. While predator control can be temporarily effective, it is often laborious and carries ethical issues. Thus, we need alternative, non-lethal methods for reducing predator impact on their prey. We performed a landscape-scale experiment to study whether two non-lethal methods could protect ground-nesting waterfowl from nests predation. We spread either non-rewarding waterfowl odour (chemical camouflage) or eggs containing an aversive agent (conditioned food aversion) in the surroundings of study wetlands located in southern Finland. Predation of artificial waterfowl nests by red foxes decreased in sites with chemical camouflage, while there was no effect on predation by invasive raccoon dogs. Food aversion created less obvious effects than the chemical camouflage, but both methods indicated potential for reducing nest predation. Based on wildlife-camera data mesopredator observations did not, however, decrease near treatment wetlands. This suggests that treatments did not reduce predator activity, but affected foraging behaviour of predators and reduced their ability to find the nests. We conclude that managers considering non-lethal methods should carefully consider the effectiveness of different methods and potential species-specific responses. Nevertheless, our study support calls for wider use of non-lethal methods in reducing predator impacts on prey. These methods offer ethical and potentially effective approaches which keep native predator fauna intact, but create protection for vulnerable prey.

Avoidance of neonicotinoid-treated seeds and cotyledons by captive eared doves (Zenaida auriculata, Columbidae)

Farmland birds can be exposed to neonicotinoids through the ingestion of treated unburied seeds and cotyledons. The aim of this study was to evaluate the avoidance of sorghum with imidacloprid, clothianidin or thiamethoxam, soybean with imidacloprid, and soybean cotyledons with imidacloprid or thiamethoxam on eared doves (Zenaida auriculata). Doves were fed with test food (untreated and neonicotinoid-treated sorghum, soybean or soybean cotyledons) and maintenance food (seed mix) for 3–5 days to study the repellency (primary repellency and conditioned aversion) and anorexia caused by neonicotinoid-treated food, followed by a 7-day period on maintenance food to study the persistence of the anorexic effect after neonicotinoid exposure. Immediately afterward, the same doves were exposed to treated test food during a second period of 3–5 days to study the potential reinforcement of food avoidance. Finally, doves were fed with untreated test food to test the capacity of the pesticide to induce conditioned food aversion against untreated food in subsequent encounters. Intoxication signs and differences of body weight were determined. With sorghum, the three neonicotinoids produced a decrease in the consumption of treated seeds by >97% compared to control birds. However, this was not enough to prevent the death of 3/8 and 1/8 of the doves exposed to imidacloprid and clothianidin, respectively. Anorexia was clearly observed with neonicotinoid-treated sorghum. The birds did not avoid the untreated sorghum after exposure to the treated sorghum, indicating that avoidance is not generalized to the type of food without an associated sensory cue. The results obtained with soybean seeds and cotyledons were less conclusive because captive doves hardly consumed these foods, even without neonicotinoid treatment. The avoidance of sorghum seeds treated with neonicotinoids was insufficient to prevent poisoning and death of eared doves.

The Role of DNA Methylation and Activity of Neurotransmitter Receptors in the Mechanisms of Specific Anterograde Amnesia and Memory Recovery.

Impairment of reconsolidation of conditioned food aversion memory led to the development of a specific anterograde amnesia: repeated training of amnestic snails did not induce long-term memory formation. DNA demethylation caused by injections of DNA methyltransferase inhibitor (DNAMT) during repeated training led to long-term memory formation. Injections of an NMDA glutamate receptor antagonist or a serotonin receptor antagonist prevented memory formation induced by administration of DNAMT inhibitor and repeated training. We hypothesize that methylation-dependent repression of neuronal genes underlies anterograde amnesia. Demethylation eliminated the blockade of these genes and created conditions for long-term memory formation, the induction mechanisms of which involve neurotransmitter receptors.

In search of the Holy Grail of Rodent control: Step-by-step implementation of safe and sustainable-by-design principles on the example of rodenticides

The field of chemical rodent control has seen no major developments in the last decades, even though anticoagulant rodenticides (AR), the mainly used substances to manage mice and rats, are known environmental pollutants and candidates for substitution under the European Biocidal Products Regulation 528/2012. Moreover, recent political developments in Europe and the USA demand more safety and sustainability in the management of chemicals, reinforcing the need for environmentally friendly substances. In this concept study, we present a step-by-step approach to improve the environmental properties of rodenticides. Repurposing of existing pharmaceuticals, the use of enantiomerically pure rodenticides, or the improvement of the formulation by microencapsulation can help to alleviate environmental problems caused by AR in the short term. Modification of the chemical structures or the development of prodrugs as medium-term strategies can further improve environmental properties of existing compounds. Ultimately, the development of new substances from scratch enables the utilisation of so far ignored modes of actions and the application of modern safe and sustainable-by-design principles to improve target specificity and reduce the negative impact on non-target organisms and the environment. Overall, our concept study illustrates the great potential for improvement in the field of chemical rodent control when applying available techniques of green and sustainable chemistry to known or potential rodenticides. Most promising in the medium term is microencapsulation that would allow for the use of acutely acting substances as it could circumvent bait shyness. On a longer timescale the de novo design of new rodenticides, which is the only method that can combine a high target specificity with good environmental properties, is the most promising approach.

Protein synthesis inhibitor administration before a reminder caused recovery from amnesia induced by memory reconsolidation impairment with NMDA glutamate receptor antagonist

Memory recovery in amnestic animals is one of the most poorly studied processes. In this paper, we examine the role of protein synthesis and a reminder in the mechanisms of amnesia and memory recovery in grape snails trained to conditioned food aversion. Amnesia was induced by the impairment of memory reconsolidation using NMDA (N-methyl d-aspartate) glutamate receptor antagonists. In an early stage of amnesia (day 3), injections of protein synthesis inhibitors into animals combined with a reminder by a conditioned stimulus (CS) led to the recovery of aversive reactions to its presentation. Two types of changes in reactions to CS were revealed. In most animals, a persistent recovery of memory retrieval was found that lasted for at least 10 days. In other snails, aversive responses to CS persisted for 24 h. Isolated injections of inhibitors, injections of inhibitors and a reminder by the learning environment (without presenting a CS), usage of a differentiating stimulus instead of a CS, or inhibitor injections after the reminder did not affect the development of amnesia. The administration of protein synthesis inhibitors and a reminder in the late period after amnesia induction (10 days) did not affect its development or caused a short-term memory recovery. We suggest that amnesia is an active process that develops over time. The reminder induces the reactivation of the amnesia process dependent on protein synthesis, while the administration of protein synthesis inhibitors leads to the impairment of amnesia reactivation and recovery of the state formed before amnesia induction (i.e., recovery of conditioned food aversion memory).

Conditioned food aversion reduces crow nest predation: An improved framework for CFA trials

The decline of numerous bird species worldwide has been attributed to increased nest predation pressure often associated with anthropogenic factors. Identifying effective management strategies to reduce nest predation is therefore a conservation priority, but tests of management strategies often lack appropriate control treatments. Conditioned Food Aversion (CFA) is a non-lethal method of predator control where distasteful or illness-inducing artificial eggs are used to deliberately deter predators from nests or eggs of vulnerable prey species. Here, we test whether CFA can reduce predation pressure by pied crow on nests using an improved experimental methodology that includes spatial and temporal controls, non-rewarding control egg treatment and concurrent predator monitoring. At the Berg River Estuary, South Africa, we monitored survival of artificial plover-type nests and predator abundance in six sites across three experimental phases (pre-treatment, treatment and post-treatment). During the treatment phase, sites received either illness-inducing (carbachol-treated) or control (water-filled) quail eggs. Our results show that artificial nests survived longer after carbachol treatment in the post-treatment phase, both when compared to the pre-treatment phase and to the control treatment. Nest cameras revealed that pied crow were responsible for nest predation and point counts demonstrated that crow abundance did not change during the study period in control or treatment sites. Together, our results indicate that carbachol treatment induces CFA and reduces artificial nest predation by pied crow, and that mechanistically CFA in crows is likely driven by learning. This study demonstrates the potential for CFA to reduce nest predation and identifies a rigorous methodology for CFA trials.

Learning against the Background of DNA Methyltransferase Inhibition Leads to the Formation of Memory That Is Resistant to Reactivation and Impairment.

The involvement of DNA methylation in the mechanisms of formation of conditioned food aversion memory was studied on Helix lucorum snails. The dynamics of aversion formation in snails injected with DNA methyltransferase inhibitor RG108 did not differ from that in control snails. The memory was retained for more than one month after training following RG108 injection and the duration of memory persistence did not differ from that in control animals. However, the characteristics of memory in control and experimental snails differed significantly. In control snails, injections of glutamate NMDA-receptor antagonist or protein synthesis inhibitor before memory retrieval caused disorders in the memory reconsolidation and development of amnesia 2 days after training. By contrast, injections of these substances before retrieval to snails trained against the background of RG108 treatment caused no memory disorders. We hypothesized that inhibition of DNA methylation processes led to the formation of strong memory, not reactivated after retrieval and not transformed into a labile state sensitive to amnesic agents.

Neuroscience: The Secret of Sauce Béarnaise Syndrome Is in the Circuit

Summary During conditioned food aversion — a.k.a. sauce bearnaise syndrome — the ingestion of a spoiled food item leads to a lasting aversion towards cues reminiscent of the item. A new study finds that, in Drosophila, taste aversion depends on the immune system and the mushroom body.

The effectiveness of conditioned aversion in wolves: Insights from experimental tests

It has been suggested that conditioned food aversion (CFA) could be a potential non-lethal intervention by which to deter attacks on livestock by large carnivores. CFA occurs when an animal associates the characteristics of a food with an illness, thus rejecting that food in subsequent encounters. CFA can be associated with an artificial odour during conditioning. Despite the debate surrounding the use of this intervention, more studies evaluating the effectiveness of CFA are necessary. We experimentally evaluated the potential of microgranulated levamisole + a vanilla odour cue to induce CFA in captive Iberian wolves (Canis lupus signatus). Four out of the five wolves treated showed an aversion to the meat for a minimum of one month after conditioning. The microgranulated presentation masked the flavour and smell of the levamisole but increased its volume, which may have facilitated its detection by the wolves. We also observed that the strength of the odour played an important role in the aversion extinction. The use of microgranulated levamisole + an odour cue has the potential to be used as an intervention by which to induce aversive conditioning in wolves in the wild, although rigorous field tests are required. We discuss the potential of CFA to deter attacks on livestock by large carnivores.

Control of Rat Damage in Oil Palm Plantation Using Local Hunting Dogs-IOI Kahang Estate’s Experience

Kahang Estate, situated in the south eastern part of Johor state is known for severe rat damage on oil palm fruits for more than two-and-a-half decades. The main species is Rattus tiomanicus and the current practice of poison baiting with high number of rounds per campaign was found to be short lived in controlling the rat damage on fresh fruit bunches. A coincidental observation on one of the harvester’s hungry mongrel dog hunting a running rat in the field gave the idea and prompted the estate management to train and establish a rat hunting dog team since 2017. The current paper shares this first of its kind experience of Kahang Estate management in controlling the rat population by dogs in a consolidated area of 364 hectares of 2009 replants. Keywords: Rattus tiomanicus, bait shyness rats, mongrel dogs.

Reducing nest predation of ground-nesting birds through conditioned food aversion

Populations of many ground-nesting bird species have declined substantially due to several factors, and predation can be a leading contributor to these declines. As a method for reducing the nest predation on ground-nesting birds, we tested whether conditioned food aversion (CFA) can reduce red-legged partridge (Alectoris rufa) nest predation by red foxes (Vulpes vulpes). With a before-after control-impact design we deployed 1329 artificial nests in two different habitats in Central Spain using thiram as an aversive. Artificial nests were monitored by camera traps to identify the red fox individuals during the predation events. 26 foxes were GPS-tagged to monitor their spatial movements and feeding behavior. Partridge density and productivity were monitored to assess the thiram treatment effect on partridge population. Thiram treatment decreased artificial nest predation by foxes in both study sites by 26.8–50.1%, but this was compensated by an increased predation by other predators, possibly enhanced by the availability of our artificial nests. 78% of identified foxes that ingested thiram-treated eggs, stopped nest predation after treatment. Foxes maintained stable territories during the whole study period. Partridge productivity was 132–677% higher in thiram-treatment areas than in control areas, and partridge density after treatment increased more in thiram-treated areas (193–292%) than in control areas (1.8–99%). Our study shows that CFA reduced ground nest predation by foxes, and had a positive effect on the partridge population despite the compensatory predation. This method could be used as a non-lethal tool for conservation of endangered ground-nesting bird species.

Techniques for prevention and control of poisoning by sodium monofluoroacetate (MFA)-containing plants in ruminants

ABSTRACT: Monofluoroacetate (MFA)-containing plants cause sudden death associated with exercise in ruminants, and are responsible for significant losses in Brazilian livestock, estimated at 500,000 bovine deaths annually. Most of the times, the control and treatment of this type of poisoning are not efficient, because disease evolution is superacute, usually causing the death of the animal. Due to the difficulty in controlling this intoxication, several studies have suggested alternatives to prevent it, mainly by making animals resistant to the MFA present in these plants or by avoiding their consumption. This literature review addresses the techniques used experimentally to control the poisoning of ruminants by plants containing MFA. The first studies carried out in Brazil demonstrated that goats and sheep that continuously receive non-toxic doses of plant containing MFA show greater resistance to poisoning than untreated animals, and that this resistance can be transmitted by ruminal fluid transfaunation, suggesting that poisoning occurs due to the presence of bacteria that hydrolyze MFA in the rumen. Based on this hypothesis, several MFA-hydrolyzing bacteria were isolated (Enterococcus faecalis, Bacillus sp., Paenibacillus sp., Burkholderia sp., Cupriavidus sp., Staphylococcus sp., Ancylobacter sp., Ralstonia sp., Stenotrophomonas sp., Pigmentiphaga kullae, and Ancylobacter dichloromethanicus). When some of these bacteria were administered intraruminally, they provided the animal with a different level of protection against poisoning. However, it was observed that protection is gradually lost when the bacterium administration is interrupted. Consequently, to obtain more efficient protection, these bacteria should be administered continuously, probably in the form of probiotics. In another assay, MFA was administered to sheep at non-toxic doses to test the hypothesis that this substance could induce the multiplication of bacteria that hydrolyze it in the rumen. There was no increase in resistance to poisoning after administration of MFA; however, no signs of poisoning were observed when animals received trifluoroacetate and no clinical signs were verified when they were challenged with toxic doses of MFA; in contrast, all control animals presented clinical signs. These results suggest that trifluoroacetate induces the proliferation of MFA-degrading bacteria, and can be used in intoxication prophylaxis. The conditioned food aversion technique, using lithium chloride, has been successfully used experimentally to prevent ruminants from ingesting plants that contain MFA. Another alternative tested was the spraying of Amorimia septentrionalis with the endophytic bacterium Herbaspirillum seropedicae, which degrades MFA, resulting in decreased concentration of this compound in the plants. In conclusion, several experimental techniques have been proved efficient in the control and prophylaxis of MFA-containing plant poisoning; however, none of these techniques are available commercially. Further experiments, mainly in the field, should be carried out to adapt some of these techniques to the conditions of extensive breeding in the numerous areas where MFA-containing plants occur.

Changes in Amnesia Parameters over Time after Long-Term Memory Disruption with Protein Kinase Mζ Inhibitor.

We studied the involvement of protein kinase Mζ (PKMζ) in the mechanisms of amnesia development within 10 days after disruption of conditioned food aversion memory with ZIP (a PKMζ inhibitor). Repeated training performed in 3 days after amnesia induction with ZIP, led to the formation of conditioned food aversion memory, but the number of combined presentations of food and reinforcer stimuli was lower than during the initial training. Repeated training performed in 10 days after amnesia induction also led to memory formation, but the number of combined presentations of the stimuli was similar to that during the initial training. It was hypothesized that at the early stages of ZIP-induced amnesia, residual memory trace can be restored and amplified during repeated training, which led to memory expression at the behavioral level. At the late stages of amnesia, this memory trace was completely erased and repeated training led to the formation of a new memory. Thus, PKMζ inhibition results in the relatively fast impairment of memory retrieval and induces long-term process of memory erasing.