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 synaptic transmission is often mediated by activation of G protein coupled receptors (GPCRs) and has been most extensively studied at amino acid-mediated synapses where ligand gated receptors mediate the postsynaptic signal. Here 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 postsynaptic potential (EPSP(M)) that was associated with a small increase in cell input resistance could be evoked in isolation. This response was enhanced by the acetylcholine (ACh) esterase inhibitor physostigmine (1 microM) and depressed by the vesicular ACh transport inhibitor vesamicol (50 microM). The mu-opioid receptor agonists DAMGO (1-5 microM) and etonitazene (100 nM), but not the delta- and kappa-opioid receptor selective agonists DTLET (1 microM) and U-50488 (1 microM), potentiated this EPSP(M) (up to 327%) without affecting cell membrane potential or input resistance; an effect that was totally reversed by naloxone (5 microM). In contrast, postsynaptic depolarizations and increases in cell input resistance evoked by carbachol (3 microM) were unaffected by DAMGO (1-5 microM) but were abolished by atropine (1 microM). Taken together these data provide good evidence for a mu-opioid receptor-mediated presynaptic enhancement of mAChR-mediated EPSPs in hippocampal CA1 pyramidal neurones.
Kearns
I R
IR
Department of Neuroscience, University of Edinburgh, 1 George Square, Scotland EH8 9JZ, Edinburgh, UK.
Morton
R A
RA
Bulters
D O
DO
Davies
C H
CH
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid