Distinct contributions of dopamine receptors in the nucleus accumbens core or shell to established cocaine reinforcement under a second-order schedule

Nucleus accumbens dopamine is implicated in the primary and conditioned reinforcing properties of abused drugs. In the present study, specific impairments in responding for intravenous cocaine (0.3 mg/inf/0.1 ml/5 s) under a fixed-ratio 1 (FR-1) or second-order schedule (FI 15 min (FR10:S)) were investigated following infusion of the dopamine antagonist, alpha-flupenthixol, into either the nucleus accumbens core or shell. Infusion of alpha-flupenthixol into the core decreased cocaine intake under the FR-1 and second-order schedules. By comparison, blockade of nucleus accumbens shell dopamine receptors increased cocaine intake under the FR-1 schedule. Under the second-order schedule, cocaine intake and the number of responses was decreased. Effects on responding were more apparent after self-administered cocaine, when impairments in the latency to receive cocaine infusions were no longer evident. These results are discussed with reference to a role for nucleus accumbens shell dopamine in instrumental responding, and a role of nucleus accumbens core dopamine in incentive motivation, perhaps under the control of contextual stimuli. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.