Enhanced reward-facilitating effects of d-amphetamine in rats in the quinpirole model of obsessive–compulsive disorder

Abstract

The underlying neurobiology of addictive or repetitive behaviours, such as obsessive-compulsive disorder (OCD), involves dopaminergic dysregulation. While addictive behaviour depends strongly on mesolimbocortical dopaminergic responses, repetitive behaviours have been associated with dopaminergic dysregulation in the basal ganglia-thalamo-cortical circuitry. The present study investigates differences in brain stimulation reward in rats with quinpirole-induced compulsive checking behaviour, in order to examine if deficits in reward processing are also relevant for OCD. Rats were tested in the intracranial self-stimulation (ICSS) paradigm, which targets reward-related responses. After phenotype induction, animals were implanted with a monopolar stimulation electrode in the left medial forebrain bundle and trained to press a lever to self-administer electric stimulation of varying frequency. The curve-shift method was used to assess the reward-facilitating effects of d-amphetamine and the reward-attenuating effects of haloperidol (a D(2) antagonist). Thresholds for ICSS were estimated before and after drug/saline injection. The reward-facilitating effects of d-amphetamine were enhanced in quinpirole-treated rats in comparison to controls. This finding suggests that chronic quinpirole-treatment induces changes within the reward circuitry relevant for compulsive behaviour in the rat.