Autoradiographic analysis of muscarinic cholinergic and serotonergic receptor alterations following methamphetamine treatment.
Autoradiographic examination of the response of muscarinic cholinergic (M1 and M2) receptors to multiple doses of methamphetamine has been performed in several regions of the rat brain. Both muscarinic receptor subtypes were identified with [3H]-N-methylscopolamine, while M1 receptors were specifically labeled with [3H]-pirenzepine. No change in muscarinic receptors labeled with [3H]-pirenzepine was found in any of the brain regions examined following methamphetamine treatment; however, [3H]-N-methylscopolamine binding was significantly reduced (24-40%). These results indicate that M1 receptors remained unchanged after the drug treatment, while M2 receptors were reduced in many areas of the rat central nervous system following multiple high doses of methamphetamine. Five doses of methamphetamine (6-hour interval between doses) were required to elicit the receptor changes in all brain regions analyzed. Within 7 days after drug treatment, the receptor number returned to control values in the affected brain areas. Additionally, the response of serotonin (5-HT1 and 5-HT2) receptors to methamphetamine was examined and found to be reduced in a few brain areas analyzed. The receptor changes were accompanied by METH-induced decreases in tyrosine hydroxylase and tryptophan hydroxylase activities.
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase