The effect of chronic ethanol consumption on muscarinic receptors in rat brain.
Ethanol (15% v/v) was administered in the drinking water to male Wistar rats over period of 3 months. Binding properties of muscarinic receptors were studied in synaptosomes from selected brain areas using [(3)H]quinuclidinyl benzilate and its displacement by the selective antagonist, pirenzepine and the agonist, carbachol. Dissociation constants (K(d)) of all three ligands in the cerebral cortex, hippocampus and striatum of ethanol-treated groups did not differ from those in controls. Density of [(3)H]quinuclidinyl benzilate binding sites in the cortex of ethanol-treated animals was approx. 50% higher than in controls (2.06 +/- 0.2 and 1.32 +/- 0.2 pmol/mg of protein respectively, mean +/- SD, n = 6, P < 0.001). This was largely attributable to an increase in M(1) binding sites as shown by pirenzepine displacement studies. In the hippocampus and striatum binding capacity of muscarinic receptors was not affected by ethanol treatment. Synthesis of acetylcholine in cerebral cortex prisms from ethanol-treated animals was not inhibited under resting conditions, but stimulation of synthesis by high K(+) concentration was significantly altenuated by comparison with controls. These results suggest that chronic ethanol consumption induces changes in cholinergic neurotransmission in selected brain areas.
Pietzak
E R
ER
Alcohol Research Unit, Department of Biochemistry, University of Queensland, St. Lucia, Qld 4067, Australia.
Wilce
P A
PA
Shanley
B C
BC