Acute ethanol dependence or long-term ethanol treatment and abstinence do not reduce hippocampal responses to carbachol.
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.
Frye
G D
GD
Department of Medical Pharmacology, Texas A&M University College of Medicine, College Station 77843-1114, USA.
Taylor
L
L
Grover
C A
CA
Fincher
A S
AS
Griffith
W H
WH
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*
D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D000431:Ethanol; D002217:Carbachol