Dataset Information

Extinction learning is slower, weaker and less context specific after alcohol.

ABSTRACT: Alcohol is frequently involved in psychological trauma and often used by individuals to reduce fear and anxiety. We examined the effects of alcohol on fear acquisition and extinction within a virtual environment. Healthy volunteers were administered alcohol (0.4g/kg) or placebo and underwent acquisition and extinction from different viewpoints of a virtual courtyard, in which the conditioned stimulus, paired with a mild electric shock, was centrally located. Participants returned the following day to test fear recall from both viewpoints of the courtyard. Skin conductance responses were recorded as an index of conditioned fear. Successful fear acquisition under alcohol contrasted with impaired extinction learning evidenced by persistent conditioned responses (Experiment 1). Participants' impairments in extinction under alcohol correlated with impairments in remembering object-locations in the courtyard seen from one viewpoint when tested from the other viewpoint. Alcohol-induced extinction impairments were overcome by increasing the number of extinction trials (Experiment 2). However, a test of fear recall the next day showed persistent fear in the alcohol group across both viewpoints. Thus, alcohol impaired extinction rather than acquisition of fear, suggesting that extinction is more dependent than acquisition on alcohol-sensitive representations of spatial context. Overall, extinction learning under alcohol was slower, weaker and less context-specific, resulting in persistent fear at test that generalized to the extinction viewpoint. The selective effect on extinction suggests an effect of alcohol on prefrontal involvement, while the reduced context-specificity implicates the hippocampus. These findings have important implications for the use of alcohol by individuals with clinical anxiety disorders.

SUBMITTER: Bisby JA

PROVIDER: S-EPMC4655873 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

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Extinction learning is slower, weaker and less context specific after alcohol.

Bisby James A JA King John A JA Sulpizio Valentina V Degeilh Fanny F Valerie Curran H H Burgess Neil N

Neurobiology of learning and memory 20150730

Alcohol is frequently involved in psychological trauma and often used by individuals to reduce fear and anxiety. We examined the effects of alcohol on fear acquisition and extinction within a virtual environment. Healthy volunteers were administered alcohol (0.4g/kg) or placebo and underwent acquisition and extinction from different viewpoints of a virtual courtyard, in which the conditioned stimulus, paired with a mild electric shock, was centrally located. Participants returned the following d ...[more]

PMID: 26234587

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Project description:Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example the expression of an aversive behavior upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinctionare only beginning to emerge. Here we show that fear extinction initiates up-regulation of hippocampal insulin-growth factor 2 (Igf2) and down-regulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2-signaling during fear extinction. To this end we show that fear extinction-induced IGF2/IGFBP7-signaling promotes the survival of 17-19 day-old newborn hippocampal neurons. In conclusion, our data suggests that therapeutic strategies that enhance IGF2-signaling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. We employed mice to investigate fear extinction in the hippocampus-dependent contextual fear conditioning paradigm. To this end, male C57BL/6J mice were exposed to the fear conditioning box (context) followed by an electric foot-shock which elicits the acquisition of conditioned contextual fear. For extinction training animals were repeatedly reexposed to the conditioned context on consecutive days (24h interval) without receiving the footshockagain (extinction trial, E). This procedure eventually results in the decline of the aversive freezing behavior. Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups. To gain a better understanding of the molecular processes underlying fear extinction we performed a genome-wide analysis of the hippocampal transcriptome during fear extinction. In the employed paradigm fear extinction is a gradual process. To capture the longitudinal course of fear extinction we decided to perform hippocampal microarray analysis at two time points: (1) After the first extinction trial (E1) when animals display high levels of aversive freezing behavior and (2) at the extinction trial on which the freezing behavior was significantly reduced when compared to E1. This extinction trial, in the case of this experiment E5, we termed “extinction trial low freezing” (ELF). Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups (3). For all three groups we hybridized 5 samples (biological replicates).

Project description:The acquired motivational impact of conditioned stimuli has been studied using the Pavlovian-to-instrumental transfer (PIT) task, where a cue paired with a reward is consistently shown to energize responses separately trained with that same reward ("specific" PIT). However, most alcohol studies have shown that alcohol-related cues elevate responses trained with either the same alcohol reward or with other non-alcoholic rewards ("general" PIT). The effects of extinction on this alcohol PIT effect have not been fully explored. We tested the hypothesis that cues signaling different-tasting alcohols might acquire specific craving reactions for those alcohols leading to specific PIT, but that these effects might be sensitive to extinction. Three experiments examined the specificity of PIT using alcohol and non-alcohol outcomes. Rats first consumed different-flavored alcohol solutions in their home cages. Then they were trained to perform two responses, each reinforced with distinctly flavored solutions, using a Polycose fading procedure. The outcomes were sweet (4% sucrose) or salty (0.9% NaCl) ethanol (10% v/v) solutions (Experiments 1 and 2) or one plain or salty alcohol vs. a non-alcoholic sweet solution (Experiment 3). Then, two cues were each differentially paired with these outcomes. In PIT tests, animals performed both responses in the presence and absence of these cues without any rewards. Experiments 1, 2, and 3 showed that a cue paired with a flavored alcohol produced a small but consistent bias toward the response trained with the same alcohol solution (specific PIT). Experiment 2 showed that extinction eliminated this effect. Experiment 3 demonstrated that specific PIT occurred when contrasting salty, or plain, alcohol to a non-alcoholic solution. These results provide evidence that alcohol-related stimuli can elicit craving for specific types of alcohol (as revealed by specific PIT), but that this effect is sensitive to extinction. This paradigm of contrasting two distinctly flavored alcohols may be an especially useful animal model of alcohol addiction.

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Extinction learning is slower, weaker and less context specific after alcohol.

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Extinction learning is slower, weaker and less context specific after alcohol.

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