title: Acute ethanol dependence or long-term ethanol treatment and abstinence do not reduce hippocampal responses to carbachol.
abstract: In the hippocampus of human alcoholics, prolonged ethanol treatment reduces the number of muscarinic ligand binding sites present at autopsy suggesting a decrease in functional muscarinic receptors. Whether these changes are due to alcohol-induced brain damage or ethanol dependence and represent a reduced level of cholinergic function is unknown. The present studies tested the impact of ethanol dependence or long-term ethanol treatment and subsequent withdrawal on the function of pre- and postsynaptic muscarinic receptors in the CA1 region of the rat hippocampus. Field excitatory postsynaptic potentials (EPSPs) were inhibited in a concentration-dependent manner by 0.1-100 microM carbachol. This presynaptic inhibitory action of carbachol involving muscarinic receptors was not significantly reduced either by ethanol treatment (12 days), causing physical dependence, or by long-term ethanol treatment (97-120 days) and abstinence (3-6 months). Postspike after hyperpolarizations (AHPs) were inhibited in a concentration-dependent manner by carbachol (6-2000 nM). This postsynaptic excitatory action of muscarinic receptors also was not significantly reduced either by 12-day ethanol treatment or by long-term ethanol treatment. Taken together, these results suggest that neither pre- nor postsynaptic muscarinic receptor function measured electrophysiologically is reduced by either ethanol dependence or long-term ethanol consumption and abstinence in the rat as suggested by reduced muscarinic ligand binding in the hippocampus of human alcoholics.
authors.affiliation: Department of Medical Pharmacology, Texas A&M University College of Medicine, College Station 77843-1114, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Frye
authors.forename: L
authors.initials: L
authors.lastname: Taylor
authors.forename: C A
authors.initials: CA
authors.lastname: Grover
authors.forename: A S
authors.initials: AS
authors.lastname: Fincher
authors.forename: W H
authors.initials: WH
authors.lastname: Griffith
mesh_terms: D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D000431:Ethanol; D002217:Carbachol