DELTA,MU AND KAPPA-OPIOID RECEPTOR AGONISTS INHIBIT DOPAMINE OVERFLOW IN RAT NEOSTRIATAL SLICES

The actions of opioid receptor agonists on stimulus evoked dopamine overflow in rat neostriatal slices were investigated using fast cyclic voltammetry. Activation of delta and mu receptors reversibly depressed striatal dopamine efflux induced by intrastriatal stimulation. The inhibitory effect of DADLE (D-Ala(2), D-Leu(5)-enkephalin, delta/mu agonist), DPDPE (D-Pen(2,5)-enkephalin, delta selective) and DALDA (D-Arg(2), Lys(4)-demorphin-(1,4)-amide, mu selective), respectively, were concentration dependent and could be blocked by application of receptor subtype selective antagonists. At a concentration of 1 mu M, the kappa receptor agonist U-50488H inhibited dopamine overflow. This effect could be partially antagonized by kappa receptor selective antagonists. Prior application of virtually ineffective concentrations (less than or equal to 0.1 mu M) of the kappa agonist reduced the efficacy of 1 mu M U-50488H suggesting a desensitization of the receptor. Since the stimulus induced dopamine overflow in striatal slices can be attributed solely to the release of dopamine from presynaptic terminals, these experiments demonstrate that delta, mu and kappa opioid receptors exert an inhibitory control on striatal dopamine release via a presynaptic mechanism.