Autoradiographic analysis of muscarinic cholinergic and serotonergic receptor alterations following methamphetamine treatment

Abstract

Autoradiographic examination of the response of muscarinic cholinergic (M 1 and M 2) 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 M 1 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 M 1 receptors remained unchanged after the drug treatment, while M 2 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-HT 1 and 5-HT 2) 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.