The influence of dopaminergic dysregulations on brain stimulation reward

Addictive as well as repetitive behaviours like in obsessive compulsive disorder (OCD) were identified to involve dopaminergic dysregulations as major neuropathologic underpinnings. While addictive behaviour depends on dopaminergic responses in the forebrain, repetitive behaviours were associated with dopaminergic dysregulations in the basal ganglia–thalamo–cortical circuitry. The present study investigates differences in brain stimulation reward in rats with genetically or pharmacologically induced dopaminergic dysregulations. DAT-overexpressing animals and rats with quinpirole induced checking behaviour were tested in an intracranial self-stimulation (ICSS) paradigm targeting reward-related forebrain responses. The experimental animals were implanted with a monopolar electrode in the left medial forebrain bundle and trained to press a lever to self-deliver electric stimulation of varying frequency. The curve-shift method was used to asses reward facilitating effects of D-amphetamine and effects of haloperidol (a D2 antagonist). After ICSS thresholds stabilized, rats received i.p. injections of vehicle, 0.5 mg/kg (high dose), 0.1 mg/kg (low dose) D-amphetamine and 0.05 mg/kg (high dose), 0.01 mg/kg (low dose) haloperidol. Thresholds for ICSS were measured before and after injection. We present the successful application of an ICSS paradigm which indicates dysregulations within different dopaminergic circuitries to be relevant for reward-related and repetitive behaviour.