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.

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