ELECTROPHYSIOLOGICAL DEMONSTRATION OF MU-OPIOID, DELTA-OPIOID AND KAPPA-OPIOID RECEPTORS IN THE VENTRAL PALLIDUM

Opioid mu, kappa and delta receptors are present in significant densit ies in the ventral pallidum (VP). To examine their contribution to VP neuronal activity, changes in firing rate during microiontophoresis of the receptor-selective agonists [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enke phalin (DAMGO) (mu), [D-Pen(2,5)]-enkephalin (DPDPE) (delta) and N-[2- (1-pyrrolidinyl)cyclohexyl]-benzene-acetamide methane sulfonate (U5048 8H) (kappa), and the antagonists D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-N H2 (CTOP) (mu) and norbinaltorphimine (kappa) were determined in chlor al hydrate-anesthetized rats. A majority of the neurons demonstrated e jection current-dependent decreases in neuronal activity to DAMGO and U50488H. The rate suppressions were attenuated by coiontophoresis of t he homotypic antagonist, indicating receptor subtype-specificity of th e responses, In contrast, DPDPE decreased firing in only 24% of the re corded neurons. In those neurons tested with all three agonists, nearl y 70% were sensitive to at least one, Among responding neurons, approx imately one-quarter was influenced by activation of all three receptor subtypes while another quarter was sensitive to only mu activation, T hus, subpopulations of VP neurons may exist according to the influence of particular opioid receptor subtypes. These findings were compared to the nonselective opioid, morphine, Morphine iontophoresis elicited both excitations and inhibitions whereas DAMGO exclusively inhibited t he same VP neurons. Responses to both were antagonized by naloxone and CTOP, indicating mu receptor-specific actions, The results are discus sed in terms of differential direct and indirect effects of morphine a nd DAMGO. In summary, mu, delta and kappa opioid receptors can indepen dently alter neuronal activity within the VP, and direct and indirect effects are most likely involved.