ACTIVATION OF MU-OPIOID RECEPTOR MODULATES GABA(A) RECEPTOR-MEDIATED CURRENTS IN ISOLATED SPINAL DORSAL HORN NEURONS

Whole-cell voltage-clamp technique was used to examine the effects of a mu-opioid receptor agonist DAGO (Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephal in) on GABA-induced currents in acutely isolated spinal dorsal horn (D H) neurons from laminae I-IV of young rats. We found that a bicucullin e-sensitive GABA-induced current was potentiated by DAGO (0.5-500 nM), in a dose-dependent manner, in similar to 62% of the tested cells. Th e elevated GABA responses outlasted the period of DAGO application, an d either recovered within 10 min after the removal of the peptide or p ersisted for up to 50 min. The potentiating effect of DAGO was reduced or prevented by naloxone and the mu-opioid receptor-selective antagon ist beta-funaltrexamine. A similar enhancing effect on the membrane cu rrents activated by administration of muscimol, a GABA(A) receptor-spe cific agonist, was produced by DAGO. In addition, a transient depressi on of GABA responses was observed in similar to 25% of the cells teste d. These results indicate that the mu opioid agonist DAGO modulates th e sensitivity of postsynaptic GABA(A) receptors in a large proportion of spinal neurons from laminae I-IV, with the major effect being facil itation. The DAGO action could contribute to the regulation of the str ength of primary afferent neurotransmission, including nociception.