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

The contribution of dopamine D-4 receptors to the discriminative stimulus effects of cocaine was evaluated by testing the selective dopamine D, receptor antagonist, L-745,870 (3-([4-(4-chlororphenyl) piperazin-1-yl] methyl)-1H-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 'D-1-like' receptor antagonist, SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2hydroxy-N-methyl H-benzo[d]naptho-{2,1-b}azepine), produced surmountable antagonism. Results suggest that dopamine D-4 receptors play 3 negligible role in cocaine's discriminative stimulus effects, and further support a critical involvement of dopamine D-1-like receptors. (C) 1998 Elsevier Science B.V.