Muscarinic and nicotinic receptor changes in the cortex and thalamus of brains of chronic alcoholics.
The cholinergic system was studied in the cortical and thalamic brain tissues obtained at autopsy from 21 chronic alcoholics and 20 controls. The age related decrease in choline acetyltransferase (ChAT) activity observed in the thalamus of control brains was not found in the corresponding brain areas of chronic alcoholics. A significant decrease in the number of muscarinic receptor binding sites was observed with age in the frontal cortex of both controls and chronic alcoholics when analysed with the nonselective muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB). A significant increase in the number of muscarinic receptor binding sites was observed in the thalamus of controls but not in chronic alcoholics. When the subjects were divided into young (19-57) years, and old (59-84 years) chronic alcoholics marked losses in the total number of muscarinic receptors as well as M1 and M2 receptor subtypes were found in the thalamus of the old group of alcoholics compared to age-matched controls. A coupling of muscarinic receptors to G proteins was observed in thalamic tissues from both controls and chronic alcoholics. Guanylyl-imidodiphosphate (Gpp(NH)p) induced a steepening and rightward shift of the carbachol/[3H]QNB displacement curves performed in membrane preparations of the thalamus from both controls and chronic alcoholics. The number of high affinity nicotinic binding sites in the frontal cortex and thalamus did not differ significantly between controls and chronic alcoholics.
Hellström-Lindahl
E
E
Department of Pharmacology, Uppsala University, Sweden.
Winblad
B
B
Nordberg
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism*
D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D002795:Choline O-Acetyltransferase; D019204:GTP-Binding Proteins