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

The actions of opioid receptor agonists on stimulus evoked dopamine ov erflow in rat neostriatal slices were investigated using fast cyclic v oltammetry. Activation of delta and mu receptors reversibly depressed striatal dopamine efflux induced by intrastriatal stimulation. The inh ibitory effect of DADLE (D-Ala(2), D-Leu(5)-enkephalin, delta/mu agoni st), DPDPE (D-Pen(2,5)-enkephalin, delta selective) and DALDA (D-Arg(2 ), Lys(4)-demorphin-(1,4)-amide, mu selective), respectively, were con centration dependent and could be blocked by application of receptor s ubtype selective antagonists. At a concentration of 1 mu M, the kappa receptor agonist U-50488H inhibited dopamine overflow. This effect cou ld be partially antagonized by kappa receptor selective antagonists. P rior 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 sti mulus induced dopamine overflow in striatal slices can be attributed s olely to the release of dopamine from presynaptic terminals, these exp eriments demonstrate that delta, mu and kappa opioid receptors exert a n inhibitory control on striatal dopamine release via a presynaptic me chanism.