Mapping of the prenatal and postnatal methamphetamine effects on D-1-like dopamine, M-1 and M-2 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 D-1-like dopamine receptors (DR), M-1 and M-2 muscarinic receptors (MR), and the total number of MR (M-1-M-5 MR) in the CNS of rats exposed to MA prenatally and in adulthood. Rat mothers were exposed to MA (5 mg/kg s.c.) or saline during the entire gestation period and their male offspring were administered in adulthood with single MA (1 mg/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 M-1, M-2, total MR, and D-1-DR were measured by autoradiography. The main effect was detected in the hippocampus with the most affected M-1 MR.
D-1-DR were decreased in motor cortex and substantia nigra. M-1 MR were decreased in caudate-putamen, dorsal hippocampus, CA1, CA3 and dentate gyms (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 M-1 MR in the CNS changes induced by prenatal and adult MA exposure.