Age-related deficits of central muscarinic cholinergic receptor function in the mouse: partial restoration by chronic piracetam treatment.
The effect of aging on muscarinic cholinergic receptor function in dissociated cell aggregates of the mouse brain was investigated using two biochemical models, i.e., carbachol-induced accumulation of inositol monophosphates and carbachol-induced desensitization of muscarinic cholinergic receptors as measured by the sequestration of specific 3H-N-methyl-scopolamine binding. While aging strongly reduced carbachol-induced inositol monophosphate accumulation, desensitization was not affected in the brains of aged animals. Chronic treatment of aged mice with the nootropic drug piracetam (500 mg/kg daily PO) significantly elevated the agonist-induced accumulation of inositol monophosphates possibly by increasing the available number of muscarinic cholinergic receptors not being in a desensitized state. The results support the hypothesis that nootropics like piracetam might act in part by restoring age-related deficits of central muscarinic cholinergic receptor function.
Stoll
L
L
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, FRG.
Schubert
T
T
Müller
W E
WE
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007700:Kinetics; D050356:Lipid Metabolism; D051379:Mice; D019832:N-Methylscopolamine; D010716:Phosphatidylinositols / Q000378:metabolism; D010889:Piracetam / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012602:Scopolamine Derivatives / Q000378:metabolism
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D002217:Carbachol; D019832:N-Methylscopolamine; D010889:Piracetam