The dopamine D4 receptor antagonist L-745,870: effects in rats discriminating cocaine from saline

Abstract

The contribution of dopamine D4 receptors to the discriminative stimulus effects of cocaine was evaluated by testing the selective dopamine D4 receptor antagonist, L-745,870 (3-([4-(4-chlororphenyl) piperazin-1-yl] methyl)-1 H-pyrrolo[2,3-b] pyridine), alone and in combination with cocaine, in rats trained to discriminate cocaine (10 mg/kg) from saline. The antagonist (1-10 mg/kg) failed to engender cocaine-appropriate responding when injected alone, and failed to modify the cocaine dose-response curve when injected as a pre-treatment; however, it reduced response rates dose-dependently. Conversely, the dopamine 'D1-like' receptor antagonist, SCH 39166 ((-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2hydroxy-N-methyl-5H-benzo[d]napth o-¿2,1-b¿azepine, produced surmountable antagonism. Results suggest that dopamine D4 receptors play a negligible role in cocaine's discriminative stimulus effects, and further support a critical involvement of dopamine D1-like receptors.