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The dopamine D2/D3 receptor agonist quinpirole increases checking-like behaviour in an operant observing response task with uncertain reinforcement: a novel possible model of OCD

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posted on 2016-02-24, 12:01 authored by D. M. Eagle, C. Noschang, L. S. d'Angelo, C. A. Noble, J. O. Day, M. L. Dongelmans, D. E. Theobald, A. C. Mar, Gonzalo Pablo Urcelay, S. Morein-Zamir, T. W. Robbins
Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder (OCD). In an established rodent model of OCD checking behaviour, quinpirole (dopamine D2/3-receptor agonist) increased checking in open-field tests, indicating dopaminergic modulation of checking-like behaviours. We designed a novel operant paradigm for rats (observing response task (ORT)) to further examine cognitive processes underpinning checking behaviour and clarify how and why checking develops. We investigated i) how quinpirole increases checking, ii) dependence of these effects on D2/3 receptor function (following treatment with D2/3 receptor antagonist sulpiride) and iii) effects of reward uncertainty. In the ORT, rats pressed an 'observing' lever for information about the location of an 'active' lever that provided food reinforcement. High- and low-checkers (defined from baseline observing) received quinpirole (0.5mg/kg, 10 treatments) or vehicle. Parametric task manipulations assessed observing/checking under increasing task demands relating to reinforcement uncertainty (variable response requirement and active-lever location switching). Treatment with sulpiride further probed the pharmacological basis of long-term behavioural changes. Quinpirole selectively increased checking, both functional observing lever presses (OLPs) and non-functional extra OLPs (EOLPs). The increase in OLPs and EOLPs was long-lasting, without further quinpirole administration. Quinpirole did not affect the immediate ability to use information from checking. Vehicle and quinpirole-treated rats (VEH and QNP respectively) were selectively sensitive to different forms of uncertainty. Sulpiride reduced non-functional EOLPs in QNP rats but had no effect on functional OLPs. These data have implications for treatment of compulsive checking in OCD, particularly for serotonin-reuptake-inhibitor treatment-refractory cases, where supplementation with dopamine receptor antagonists may be beneficial.

History

Citation

Behavioural Brain Research, 2014, 264, pp. 207-229

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Neuroscience, Psychology and Behaviour

Version

  • VoR (Version of Record)

Published in

Behavioural Brain Research

Publisher

Elsevier

issn

0166-4328

eissn

1872-7549

Copyright date

2014

Available date

2016-02-24

Publisher version

http://www.sciencedirect.com/science/article/pii/S0166432813007894

Language

en