Cocaine self-administration experiments were designed to assess the respective roles of D1-like and D2-like dopamine receptors in the ventral forebrain in cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were microinjected into the nucleus accumbens core, nucleus accumbens shell, neostriatum or lateral septum prior to sessions in which cocaine was self-administered under a progressive ratio schedule by rats. The results indicated that administration of a D1/5 (SCH-23390) or a D2/D3/D4 (eticlopride), but not a D3 (U99194A) or D4 (L-750,667), dopamine receptor antagonist into the core and shell of the nucleus accumbens decreased the reinforcing efficacy of cocaine. However, in control experiments intra-accumbal core administration of SCH-23390 or eticlopride decreased food self-administration, whereas administration of these drugs into the accumbens shell had no effect on food reinforcement. Neither SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into the neostriatum or lateral septum. Collectively, these results indicate that D1-like and D2 dopamine receptors in the nucleus accumbens shell selectively modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine receptors in the accumbens core have a more general influence on reinforced behaviors.