Optimized protocol for conditioned place avoidance learning in juvenile zebrafish.
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ABSTRACT:
SUBMITTER: Palumbo F
PROVIDER: S-EPMC8065339 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Zebrafish are becoming one of the most used vertebrates in developmental and biomedical research. Fish are commonly killed at the end of an experiment with an overdose of tricaine methanesulfonate (TMS, also known as MS-222), but to date little research has assessed if exposure to this or other agents qualifies as euthanasia (i.e. a "good death"). Alternative agents include metomidate hydrochloride and clove oil. We use a conditioned place avoidance paradigm to compare aversion to TMS, clove oil, and metomidate hydrochloride. Zebrafish (n = 51) were exposed to the different anaesthetics in the initially preferred side of a light/dark box. After exposure to TMS zebrafish spent less time in their previously preferred side; aversion was less pronounced following exposure to metomidate hydrochloride and clove oil. Nine of 17 fish exposed to TMS chose not to re-enter the previously preferred side, versus 2 of 18 and 3 of 16 refusals for metomidate hydrochloride and clove oil, respectively. We conclude that metomidate hydrochloride and clove oil are less aversive than TMS and that these agents be used as humane alternatives to TMS for killing zebrafish.
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Project description:Broiler breeders, the parent stock of meat chickens, are feed-restricted throughout the production cycle to avoid obesity-related problems in their health and reproductive performance. Broiler breeders often show signs of chronic hunger, lack of satiety and feeding frustration, and the development of alternative feeding strategies has investigated the inclusion of calcium propionate (CaP) as an appetite suppressant. The mechanisms involved in the reduction of voluntary feed intake are unknown, but are thought to be due to low palatability, gastrointestinal discomfort, or both. The objective of this experiment was to examine the effect of CaP as an appetite suppressant on the experience of a negative affective state, using a conditioned place preference test. Twenty four broiler breeders were trained to associate the consumption of CaP or a placebo pill with a red or blue place, depending on inherent colour preference. Pullets consumed two pills followed by 20 g feed allotment. The CaP pill contained 160 mg of CaP and the placebo pill had 160 mg of feed. Conditioning lasted for 90 min/pullet/day over 8 consecutive days at 7 and 9 weeks of age, and pullets' choice was tested in a T-maze twice on two consecutive days at both 8 and 10 weeks of age. Data were analysed using a linear mixed regression model, with pen nested in the model and age as a repeated measure. Pullets were less likely to choose the place conditioned with the consumption of CaP (P<0.05) and the preference of the placebo linearly increased with training sessions (P<0.05). These results suggest that calcium propionate as an appetite suppressant can induce a negative affective state, reducing feed intake in broiler breeders fed CaP diets by causing an avoidance response rather than satiety.
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Project description:Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effective results obtained by using biased procedures. Zebrafish have also been used as a model system to identify factors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment. Zebrafish preference was corroborated by behavioral analysis of several indicators of drug preference, such as time spent in the drug-paired side, number of entries to the drug-paired side, and distance traveled. These results provided strong evidence that zebrafish may actually develop a preference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecular studies. Reverse transcription-quantitative real-time PCR analysis depicted a significant increase in the expression of ?7 and ?6 but not ?4 and ?2 subunits of the nicotinic receptor in nicotine-paired zebrafish brains. In contrast, zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicator of neural activity, accompanied the acquisition of nicotine-CPP. Our studies offered an incremental value to the drug addiction field, because they further describe behavioral features of CPP to nicotine in zebrafish. The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine. Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates.
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Project description:Biogenic amines are widely characterized in pathways evaluating reward and punishment, resulting in appropriate aversive or appetitive responses of vertebrates and invertebrates. We utilized the honey bee model and a newly developed spatial avoidance conditioning assay to probe effects of biogenic amines octopamine (OA) and dopamine (DA) on avoidance learning. In this new protocol non-harnessed bees associate a spatial color cue with mild electric shock punishment. After a number of experiences with color and shock the bees no longer enter the compartment associated with punishment. Intrinsic aspects of avoidance conditioning are associated with natural behavior of bees such as punishment (lack of food, explosive pollination mechanisms, danger of predation, heat, etc.) and their association to floral traits or other spatial cues during foraging. The results show that DA reduces the punishment received whereas octopamine OA increases the punishment received. These effects are dose-dependent and specific to the acquisition phase of training. The effects during acquisition are specific as shown in experiments using the antagonists Pimozide and Mianserin for DA and OA receptors, respectively. This study demonstrates the integrative role of biogenic amines in aversive learning in the honey bee as modeled in a novel non-appetitive avoidance learning assay.
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Project description:Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated context (Avoiders), or do not (Non-Avoiders). Weighted genome correlational network analysis showed that increased expression of oxidative phosphorylation-associated gene transcripts and decreased expression of gene transcripts for axon guidance and insulin signaling were associated with avoidance behavior. Based on these data, in Experiment 2, we hypothesized that Avoiders would exhibit elevated hippocampal (HPC) ROS production and degraded object pattern separation (OPS) compared with Nonavoiders. Stress impaired pattern separation performance in Non-Avoider and Avoider rats compared with nonstressed Controls, but surprisingly, Avoiders exhibited partly preserved pattern separation performance and significantly lower ROS production compared with Non-Avoiders. Lower ROS production was associated with better OPS performance in Stressed rats, but ROS production was not associated with OPS performance in Controls. These results suggest a strong negative association between HPC ROS production and pattern separation after stress, and that stress effects on these outcome variables may be associated with avoidance of a stress-paired context.
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Project description:Psychostimulants target the dopamine transporter (DAT) to elicit their psychomotor actions. Bile acids (BAs) can also bind to DAT and reduce behavioral responses to cocaine, suggesting a potential therapeutic application of BAs in psychostimulant use disorder. Here, we investigate the potential of BAs to decrease drug-primed reinstatement when administered during an abstinence phase. To do this, after successful development of cocaine-associated contextual place preference (cocaine CPP), cocaine administration was terminated, and animals treated with vehicle or obeticholic acid (OCA). When preference for the cocaine-associated context was extinguished, mice were challenged with a single priming dose of cocaine, and reinstatement of cocaine-associated contextual preference was measured. Animals treated with OCA demonstrate a significantly lower reinstatement for cocaine CPP. OCA also impairs the ability of cocaine to reduce the clearance rate of electrically stimulated dopamine release and diminishes the area under the curve (AUC) observed with amperometry. Furthermore, the AUC of the amperometric signal positively correlates with the reinstatement index. Using operant feeding devices, we demonstrate that OCA has no effect on contextual learning or motivation for natural rewards. These data highlight OCA as a potential therapeutic for cocaine use disorder.
| S-EPMC10435481 | biostudies-literature
Project description:Salient but aversive stimuli inhibit the majority of dopamine (DA) neurons in the ventral tegmental area (VTA) and cause conditioned place aversion (CPA). The cellular mechanism underlying DA neuron inhibition has not been investigated and the causal link to behavior remains elusive. Here, we show that GABA neurons of the VTA inhibit DA neurons through neurotransmission at GABA(A) receptors. We also observe that GABA neurons increase their firing in response to a footshock and provide evidence that driving GABA neurons with optogenetic effectors is sufficient to affect behavior. Taken together, our data demonstrate that synaptic inhibition of DA neurons drives place aversion.
| S-EPMC6690362 | biostudies-literature
Project description:Finding genetic polymorphisms and mutations linked to addictive behavior can provide important targets for pharmaceutical and therapeutic interventions. Forward genetic approaches in model organisms such as zebrafish provide a potentially powerful avenue for finding new target genes. In order to validate this use of zebrafish, the molecular nature of its reward system must be characterized. We have previously reported the use of cocaine-induced conditioned place preference (CPP) as a reliable method for screening mutagenized fish for defects in the reward pathway. Here we test if CPP in zebrafish involves the dopaminergic system by co-treating fish with cocaine and dopaminergic antagonists. Sulpiride, a potent D2 receptor (DR2) antagonist, blocked cocaine-induced CPP, while the D1 receptor (DR1) antagonist SCH23390 had no effect. Acute cocaine exposure also induced a rise in the expression of tyrosine hydroxylase (TH), an important enzyme in dopamine synthesis, and a significant decrease in the expression of elongation factor 1? (EF1?), a housekeeping gene that regulates protein synthesis. Cocaine selectively increased the ratio of TH/EF1? in the telencephalon, but not in other brain regions. The cocaine-induced change in TH/EF1? was blocked by co-treatment with sulpiride, but not SCH23390, correlating closely with the action of these drugs on the CPP behavioral response. Immunohistochemical analysis revealed that the drop in EF1? was selective for the dorsal nucleus of the ventral telencephalic area (Vd), a region believed to be the teleost equivalent of the striatum. Examination of TH mRNA and EF1? transcripts suggests that regulation of expression is post-transcriptional, but this requires further examination. These results highlight important similarities and differences between zebrafish and more traditional mammalian model organisms.
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Project description:The Active Allothetic Place Avoidance task is an alternative setup to Morris Water Maze that allows studying spatial memory in a dynamic world in the presence of conflicting information. In this task, a rat, freely moving on a rotating circular arena, has to avoid a sector defined within the room frame where shocks are presented. While for Morris Water Maze several studies have identified animal strategies which specifically affect performance, there were no such studies for the Active Allothetic Place Avoidance task. Using standard machine learning methods, we were able to reveal for the first time, to the best of our knowledge, explainable strategies that the animals employ in this task and demonstrate that they can provide a high-level interpretation for performance differences between an animal group treated with silver nanoparticles (AgNPs) and the control group.
| S-EPMC9314408 | biostudies-literature
Project description:Comparisons of hippocampi of Syracuse High Avoidance (SHA) and Syracuse Low Avoidance (SLA) learning rats Keywords: other
2003-12-31 | GSE932 | GEO