OPPOSITE EFFECTS OF DOPAMINE D-2 AND D-3 RECEPTORS ON LEARNING MEMORYIN THE RAT

Mesolimbocortical dopamine plays a role in learning and memory. The sp ecific receptor subtypes mediating the effects of dopamine, however, a re still unknown. Dopamine D-2, D-3 and D-4 receptors are expressed in the hippocampus and dopamine D-3 receptors are present in the septal area, suggesting that these receptor subtypes can contribute to the be havioral effects of dopamine D-2-like receptor agonists. We now invest igated the role of dopamine D-2 and D-3 receptors in learning and memo ry by using the transient amnesia induced by scopolamine in the passiv e avoidance test as experimental model. The data strongly suggest that both dopamine D-2 and D-3 receptors mediate the effects of dopamine o n the integrative function of learning and memory. In particular, we s how that the non-selective dopamine agonist apomorphine prevents the s copolamine-induced disruption of consolidation uf the previously acqui red passive avoidance behavior. This effect is mediated by receptors b elonging to the dopamine D-2 family since it was antagonized by (-)-su lpiride and mimicked by quinpirole. Nafadotride, a relatively selectiv e antagonist for dopamine D-3 receptors, antagonized scopolamine-induc ed memory disruption and potentiated the facilitatory effect of quinpi role. Taken together, these results suggest that the effects of dopami ne on memory consolidation are the result of a balance between dopamin e D-2 receptor-mediated facilitation and dopamine D-3 receptor-mediate d inhibition, and that dopamine D-2 and D-3 receptors play opposite ro les in the control of the mechanisms leading to memory consolidation. (C) 1997 Elsevier Science B.V.