Dissociable dopaminergic and pavlovian influences in goal-trackers and sign-trackers on a model of compulsive checking in OCD

Author:

Eagle D. M.,Schepisi C.,Chugh S.,Desai S.,Han S. Y. S.,Huang T.,Lee J. J.,Sobala C.,Ye W.,Milton A. L.ORCID,Robbins T. W.

Abstract

Abstract Rationale Checking is a functional behaviour that provides information to guide behaviour. However, in obsessive-compulsive disorder (OCD), checking may escalate to dysfunctional levels. The processes underpinning the transition from functional to dysfunctional checking are unclear but may be associated with individual differences that support the development of maladaptive behaviour. We examined one such predisposition, sign-tracking to a pavlovian conditioned stimulus, which we previously found associated with dysfunctional checking. How sign-tracking interacts with another treatment with emerging translational validity for OCD-like checking, chronic administration of the dopamine D2 receptor agonist quinpirole, is unknown. Objectives We tested how functional and dysfunctional checking in the rat observing response task (ORT) was affected by chronic quinpirole administration in non-autoshaped controls and autoshaped animals classified as sign-trackers or goal-trackers. Methods Sign-trackers or goal-trackers were trained on the ORT before the effects of chronic quinpirole administration on checking were assessed. Subsequently, the effects on checking of different behavioural challenges, including reward omission and the use of unpredictable reinforcement schedules, were tested. Results Prior autoshaping increased checking. Sign-trackers and goal-trackers responded differently to quinpirole sensitization, reward omission and reinforcement uncertainty. Sign-trackers showed greater elevations in dysfunctional checking, particularly during uncertainty. By contrast, goal-trackers predominantly increased functional checking responses, possibly in response to reduced discrimination accuracy in the absence of cues signalling which lever was currently active. Conclusions The results are discussed in terms of how pavlovian associations influence behaviour that becomes compulsive in OCD and how this may be dependent on striatal dopamine D2 receptors.

Funder

Wellcome Trust

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology

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