Opioid receptor-mediated control of acetylcholine release in human neocortex tissue

The effects of various opioid receptor agonists and antagonists on evoked acetylcholine release were studied in slices of human neocortex prelabelled with [³H]-choline, superfused and depolarized electrically (2 min, 3 Hz, 2 ms, 24 mA) or by K⁺ (20 mM). The -opioid receptor agonist DPDPE and the -opioid receptor agonist U50488 reduced the evoked [³H]-overflow (acetylcholine release) in a concentration-dependent fashion; the -opioid receptor antagonist naltrindole and the the -opioid receptor antagonist norbinaltorphimine, respectively, antagonized these effects. Application of the -opioid receptor agonist DAGO also resulted in an inhibition of acetylcholine release; however, both - and -opioid receptor antagonists were able to block this effect. The -opioid receptor agonists morphine and (+)-nortilidine had no effect. These results indicate that acetylcholine release in human neocortex is inhibited through - and -opioid receptors, but not through -opioid receptors.Acetylcholine release was significantly increased by the -opioid receptor antagonist naltrindole in the presence of a mixture of peptidase inhibitors providing evidence for a -opioid receptor-mediated inhibition of acetylcholine release by endogenous enkephalin.K⁺-evoked acetylcholine release in the presence of TTX was inhibited by U50488, but not by DPDPE, suggesting the presence of -opioid receptors on cholinergic terminals and the localization of -receptors on cortical interneurons. Therefore, the potent effect of DPDPE on acetylcholine release is likely to be indirect, by modulation of intrinsic cortical neurons. These interneurons probably do not use GABA as neurotransmitter since both GABA_A and GABA_B receptor agonists (muscimol and baclofen, respectively) were without effect on acetylcholine release.