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.

Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking

“…Voluntary drinking and preference for alcohol were assessed using an intermittent two- bottle-choice paradigm. Mice from both groups showed a mild pattern of escalation on alcohol consumption as previously shown in the literature [ 32 – 34 ]. D1-Lrrk2-KO mice showed increased alcohol drinking (Fig.…”

Trait sensitivity to negative feedback in rats is associated with increased expression of serotonin 5-HT2A receptors in the ventral hippocampus

“…Throughout the experiment, rats were mildly food restricted to 85% of their free-feeding weight (according to the normal growth curve recommended by the laboratory rodent supplier - Charles River Research Models and Services Catalogue) by providing 15 g of food pellets/rat/day (standard laboratory chow). The food restriction used in our study is a standard and broadly applied procedure in experiments using operant conditioning techniques allowing to maintain motivation and performance of the experimental animals ( Rygula et al, 2013 ; Cieslik et al, 2022 ; Surowka et al, 2022 ). Water was always available ad libitum .…”

Trait sensitivity to negative feedback determines the effects of chronic stress and chronic mirtazapine treatment on anxiety and stress-coping strategies in rats

“…The other regards the food restriction procedure applied in our study, which could have resulted in the social hierarchy's dependent access to the food and by that confounded the investigated traits. This however seems unlikely as the food restriction procedure used in the present study is widely applied in studies using operant conditioning and has been validated in several previous studies focused on sensitivity to feedback (Noworyta-Sokolowska et al 2019;Surowka et al 2020;Drozd et al 2019;Rychlik et al 2017;Noworyta and Rygula 2021;Cieslik et al 2022). Most importantly, however, the division of animals has been made based on their sensitivity to NF, which is based on their reaction to perceived failure (probabilistic lose-shift behavior in the PRL), and not based on their sensitivity to a reward.…”