Dataset Information

Trait sensitivity to negative feedback determines the intensity of compulsive alcohol seeking and taking in male rats.

ABSTRACT:

Background

Alcohol use disorder is one of the most common psychiatric disorders, and it is a leading cause of mortality worldwide. It has been demonstrated previously that people with alcohol use disorder are less sensitive to the negative outcomes of their actions and less able to use negative feedback to guide and adjust their ongoing behaviour. However, far less is known about the aberrant processing of negative feedback before the onset of alcohol use disorder. In this study, we investigated the theoretical claim that sensitivity to negative feedback - as a stable and enduring behavioural trait - can predict vulnerability to the development of compulsive alcohol consumption in rats.

Methods

We trained and tested rats in a series of probabilistic reversal learning tests, and based on this "negative feedback sensitivity screening," we classified each rat as more or less sensitive to negative feedback. Then, in the intermittent-access 2-bottle choice paradigm, we measured alcohol consumption in the animals classified above. In the next step, using the instrumental second-order chained schedule of alcohol reinforcement task, we examined the influence of sensitivity to negative feedback on the development of compulsive alcohol seeking behaviour. Finally, we measured how trait sensitivity to negative feedback affected the extinction and reinstatement of alcohol seeking after a period of abstinence.

Results

Trait sensitivity to negative feedback predicted the vulnerability of rats to the development of compulsive alcohol seeking and consumption. We also found significant differences between the more sensitive and less sensitive groups in their propensity to extinguish alcohol seeking behaviours when the alcohol was no longer available.

Limitations

The findings from our study did not answer the question of whether individual differences in sensitivity to negative feedback have a genetic basis or develop in response to postnatal experiences.

Conclusion

The results of our study suggest that negative feedback sensitivity screening could be used to evaluate individual vulnerability to the development and maintenance of alcohol use disorder.

SUBMITTER: Cieslik A

PROVIDER: S-EPMC9299933 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionAlcohol use disorder (AUD) is one of the most common psychiatric disorders and a leading cause of mortality worldwide. While the pathophysiology underlying AUD is relatively well known, the cognitive mechanisms of an individual's susceptibility to the development of alcohol dependence remain poorly understood. In this study, we investigated the theoretical claim that sensitivity to positive feedback (PF), as a stable and enduring behavioural trait, can predict individual susceptibility to the acquisition and maintenance of alcohol-seeking behaviour in rats.MethodsTrait sensitivity to PF was assessed using a series of probabilistic reversal learning tests. The escalation of alcohol intake in rats was achieved by applying a mix of intermittent free access and instrumental paradigms of alcohol drinking. The next steps included testing the influence of sensitivity to PF on the acquisition of compulsive alcohol-seeking behaviour in the seeking-taking punishment task, measuring motivation to seek alcohol, and comparing the speed of extinction and reinstatement of alcohol-seeking after a period of abstinence between rats expressing trait insensitivity and sensitivity to PF. Finally, trait differences in the level of stress hormones and in the expression of genes and proteins in several brain regions of interest were measured to identify potential physiological and neuromolecular mechanisms of the observed interactions.ResultsWe showed that trait sensitivity to PF in rats determines the level of motivation to seek alcohol following the experience of its negative consequences. They also revealed significant differences between animals classified as insensitive and sensitive to PF in their propensity to reinstate alcohol-seeking behaviours after a period of forced abstinence. The abovementioned effects were accompanied by differences in blood levels of stress hormones and differences in the cortical and subcortical expression of genes and proteins related to dopaminergic, serotonergic, and GABAergic neurotransmission.ConclusionTrait sensitivity to PF can determine the trajectory of alcohol addiction in rats. This effect is, at least partially, mediated via distributed physiological and molecular changes within cortical and subcortical regions of the brain.