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The development of compulsive coping behavior depends on dorsolateral striatum dopamine-dependent mechanisms.

Published version
Peer-reviewed

Repository DOI


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Authors

Marti-Prats, Lucia 
Giuliano, Chiara 
Domi, Ana 
Puaud, Mickaël 
Peña-Oliver, Yolanda 

Abstract

Humans greatly differ in how they cope with stress, a natural behavior learnt through negative reinforcement. Some individuals engage in displacement activities, others in exercise or comfort eating, and others still in alcohol use. Across species, adjunctive behaviors, such as polydipsic drinking, are used as a form of displacement activity that reduces stress. Some individuals, in particular those that use alcohol to self-medicate, tend to lose control over such coping behaviors, which become excessive and compulsive. However, the psychological and neural mechanisms underlying this individual vulnerability have not been elucidated. Here we tested the hypothesis that the development of compulsive adjunctive behaviors stems from the functional engagement of the dorsolateral striatum (DLS) dopamine-dependent habit system after a prolonged history of adjunctive responding. We measured in longitudinal studies in male Sprague Dawley rats the sensitivity of early established vs compulsive polydipsic water or alcohol drinking to a bilateral infusion into the anterior DLS (aDLS) of the dopamine receptor antagonist α-flupentixol. While most rats acquired a polydipsic drinking response with water, others only did so with alcohol. Whether drinking water or alcohol, the acquisition of this coping response was insensitive to aDLS dopamine receptor blockade. In contrast, after prolonged experience, adjunctive drinking became dependent on aDLS dopamine at a time when it was compulsive in vulnerable individuals. These data suggest that habits may develop out of negative reinforcement and that the engagement of their underlying striatal system is necessary for the manifestation of compulsive adjunctive behaviors.

Description

Keywords

Humans, Male, Rats, Animals, Dopamine, Coping Skills, Rats, Sprague-Dawley, Compulsive Behavior, Corpus Striatum, Ethanol, Water

Journal Title

Mol Psychiatry

Conference Name

Journal ISSN

1359-4184
1476-5578

Volume Title

28

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (MR/W019647/1)
Medical Research Council (MR/N02530X/1)
Brain & Behavior Research Foundation (NARSAD) (27353)
Leverhulme Trust (ECF-2018-713)
Isaac Newton Trust (18.08(g))
This work, carried out at the department of Psychology of the University of Cambridge, was funded by a UKRI grant to DB (MR/W019647/1), a UKRI grant (MR/N02530X/1) to BJE and DB, a Brain and Behavior Research Foundation NARSAD Young Investigator Grant (RG95599 Grant ID: 27353) to CG, and a Leverhulme Trust Early Career (ECF-2018-713) and Isaac Newton Trust fellowship (18.08(g)) to LMP.