OPIOID RECEPTOR-MEDIATED CONTROL OF ACETYLCHOLINE-RELEASE IN HUMAN NEOCORTEX TISSUE

The effects of various opioid receptor agonists and antagonists on evo ked acetylcholine release were studied in slices of human neocortex pr elabelled with [H-3]-choline, superfused and depolarized electrically (2 min, 3 Hz, 2 ms, 24 mA) or by K+ (20 mM). The delta-opioid receptor agonist DPDPE and the kappa-opioid receptor agonist U50488 reduced th e evoked [H-3]-overflow (acetylcholine release) in a concentration-dep endent fashion; the delta-opioid receptor antagonist naltrindole and t he the kappa-opioid receptor antagonist norbinaltorphimine, respective ly, antagonized these effects. Application of the mu-opioid receptor a gonist DAGO also resulted in an inhibition of acetylcholine release; h owever, both delta- and kappa-opioid receptor antagonists were able to block this effect. The mu-opioid receptor agonists morphine and (+)-n ortilidine had no effect. These results indicate that acetylcholine re lease in human neocortex is inhibited through delta- and kappa-opioid receptors, but not through mu-opioid receptors. Acetylcholine release was significantly increased by the delta-opioid receptor antagonist na ltrindole in the presence of a mixture of peptidase inhibitors providi ng evidence for a delta-opioid receptor-mediated inhibition of acetylc holine release by endogenous enkephalin. K+-evoked acetylcholine relea se in the presence of TTX was inhibited by U50488, but not by DPDPE, s uggesting the presence of kappa-opioid receptors on cholinergic termin als and the localization of delta-receptors on cortical interneurons. Therefore, the potent effect of DPDPE on acetylcholine release is like ly to be indirect, by modulation of intrinsic cortical neurons. These interneurons probably do not use GABA as neurotransmitter since both G ABA(A) and GABA(B) receptor agonists (muscimol and baclofen, respectiv ely) were without effect on acetylcholine release.