Opioid receptor regulation of muscarinic acetylcholine receptor-mediated synaptic responses in the hippocampus

A common feature of many synapses is their regulation by neurotransmitters other than those released from the presynaptic terminal. This aspect of syn aptic transmission is often mediated by activation of G protein coupled rec eptors (GPCRs) and has been most extensively studied at amino acid-mediated synapses where ligand gated receptors mediate the postsynaptic signal. Her e we have investigated how opioid receptors modulate synaptic transmission mediated by muscarinic acetylcholine receptors (mAChRs) in hippocampal CA1 pyramidal neurones. Using a cocktail of glutamate and gamma -amino-butyric acid (GABA) receptor antagonists a slow pirenzepine-sensitive excitatory po stsynaptic potential (EPSPM) that was associated with a small increase in c ell input resistance could be evoked in isolation. This response was enhanc ed by the acetylcholine (ACh) esterase inhibitor physostigmine (1 muM) and depressed by the vesicular ACh transport inhibitor vesamicol (50 muM). The mu -opioid receptor agonists DAMGO (1-5 muM) and etonitazene (100 nM), but not the delta- and kappa -opioid receptor selective agonists DTLET (1 muM) and U-50488 (1 muM), potentiated this EPSPM (up to 327%) without affecting cell membrane potential or input resistance; an effect that was totally rev ersed by naloxone (5 muM). In contrast, postsynaptic depolarizations and in creases in cell input resistance evoked by carbachol (3 muM) were unaffecte d by DAMGO (1-5 muM) but were abolished by atropine (1 muM). Taken together these data provide good evidence for a mu -opioid receptor-mediated presyn aptic enhancement of mAChR-mediated EPSPs in hippocampal CA1 pyramidal neur ones. (C) 2001 Elsevier Science Ltd. All rights reserved.