The cyclic AMP efflux from rat neostriatal slices induced by simultaneous activation of D-1 (stimulatory) and D-2 (inhibitory) dopamine receptors with 30 microM dopamine was inhibited by morphine (0.3-3 microM), [D-Ala2, D-Leu5]enkephalin (DADLE, 0.03-0.3 microM) but not by [D-Pen2, D-Pen5]enkephalin (DPDPE, 0.03-0.3 microM). The inhibitory effects were abolished by naloxone (0.1 microM). Upon selective D-1 dopamine receptor activation with 30 microM dopamine in the presence of 10 microM of the D-2 dopamine receptor antagonist (-)sulpiride, the enhanced efflux of cyclic AMP was reduced by all three opioid receptor agonists, but only the effect of morphine was antagonized by 0.1 microM naloxone. These data suggest that the cyclic AMP production induced in rat neostriatum by simultaneous D-1 and D-2 dopamine receptor activation may be inhibited through mu-opioid receptors, whereas on blockade of D-2 dopamine receptors both mu- and delta-opioid receptors may be linked to adenylate cyclase in an inhibitory fashion.