THE DOPAMINE D-4 RECEPTOR ANTAGONIST L-745,870 - EFFECTS IN RATS DISCRIMINATING COCAINE FROM SALINE

The contribution of dopamine D-4 receptors to the discriminative stimu lus 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 wi th cocaine, in rats trained to discriminate cocaine (10 mg/kg) from sa line. The antagonist (1-10 mg/kg) failed to engender cocaine-appropria te responding when injected alone, and failed to modify the cocaine do se-response curve when injected as a pre-treatment: however, it reduce d response rates dose-dependently. Conversely, the dopamine 'D-1-like' receptor antagonist, SCH 39166 ,7,7a,8,9,13b-hexahydro-3-chloro-2hydr oxy-N-methyl H-benzo[d]naptho-{2,1-b}azepine), produced surmountable a ntagonism. Results suggest that dopamine D-4 receptors play 3 negligib le role in cocaine's discriminative stimulus effects, and further supp ort a critical involvement of dopamine D-1-like receptors. (C) 1998 El sevier Science B.V.