MANIPULATION OF DOPAMINERGIC ACTIVITY IN THE NUCLEUS ACCUMBENS CORE PRODUCES DOSE-DEPENDENT CHANGES IN FUNCTIONAL AND DYSFUNCTIONAL CHECKING BEHAVIOUR ON THE OBSERVING RESPONSE TASK

Aims: Obsessive-compulsive disorder (OCD) is associated with alterations in the activity of corticostriatalthalamocortical circuits, including circuits encompassing the ventral striatum. Given the evidence that dopaminergic signalling in the nucleus accumbens core (NAcC) influences instrumental action selection, we sought to determine the impact of dopaminergic drugs administered to the NAcC on functional and dysfunctional checking behaviours within the Observing Response Task (ORT), a rodent analogue of compulsive-like checking in OCD.
Methods: Thirty-nine male Lister Hooded rats were trained and tested on the ORT and underwent cannulation of the NAcC. Based on prior work demonstrating that animals classified as sign-trackers show elevated levels of maladaptive checking, rats were pre-screened using a pavlovian autoshaping task. Once ORT responding was stable, animals were infused with saline or different concentrations (5, 10, 15 μg/μl) of either d-amphetamine or a-flupenthixol in a Latin-Square design to assess subsequent changes in functional and dysfunctional checking behaviour.
Results: Intracerebral administration of d-amphetamine dose-dependently increased checking whereas infusion of a-flupenthixol reduced checking behaviour, as well as locomotor activity more generally.
Conclusions: Findings revealed augmenting effects of d-amphetamine on both functional and dysfunctional checking behaviour on the ORT akin to elevated dopamine levels being associated with maladaptive checking in clinical OCD. a-flupenthixol reduced checking, but also motivated behaviour more generally. These data indicate that dopaminergic signalling within the NAcC is sufficient to increase checking, but that other regions within the corticostriatalthalamocortical circuitry are necessary for producing functional versus dysfunctional checking patterns, too.