Mapping of the prenatal and postnatal methamphetamine effects on D1-like dopamine, M1 and M2 muscarinic receptors in rat central nervous system

Abstract

Methamphetamine (MA) is worldwide known drug with high potential for addiction that causes dopamine, noradrenaline and serotonin release. MA is also able to increase acetylcholine levels in adult rodents. The aim of this study was to map changes in D1-like dopamine receptors (DR), M1 and M2 muscarinic receptors (MR), and the total number of MR (M1-M5 MR) in the CNS of rats exposed to MA prenatally and in adulthood. Rat mothers were exposed to MA (5mg/kg s.c.) or saline during the entire gestation period and their male offspring were administered in adulthood with single MA (1mg/kg) or saline injection. Thus, the animals were divided into 4 groups: prenatally MA-exposed rats treated with saline (MA/S) or MA (MA/MA) in adulthood and prenatally saline-exposed rats treated with saline (S/S) or MA (S/MA) in adulthood. One hour after the acute treatment animals were sacrificed and their brains were removed. The numbers of M1, M2, total MR, and D1-DR were measured by autoradiography. The main effect was detected in the hippocampus with the most affected M1 MR. D1-DR were decreased in motor cortex and substantia nigra. M1MR were decreased in caudate-putamen, dorsal hippocampus, CA1, CA3 and dentate gyrus (DG). M2MR were decreased in DG only. Total number of MR was moreover decreased in dorsal hippocampus, CA1, CA3 and DG. Our results have shown different patterns of changes in DR and MR, suggesting a pilot role of M1 MR in the CNS changes induced by prenatal and adult MA exposure.