CHANGES IN MONOAMINE-OXIDASE ACTIVITY IN MOUSE-BRAIN ASSOCIATED WITH D-METHAMPHETAMINE DEPENDENCE AND WITHDRAWAL

The long-term effects of d-methamphetamine (MP, 5 mg/kg) on brain mito chondrial monoamine oxidase (MAO) activity were studied in mice given MP intraperitoneally daily for 4 weeks. The MAO activities decreased w hen serotonin (5-HT) and dopamine (DA) were used as substrates. A mark ed elevation in MAO activity was seen during MP withdrawal when 5-HT, DA, beta-phenylethylamine (beta-PEA) and norepinephrine (NE) were used as substrates. The kinetics of MAO showed a significant decrease in K (m) values. but no significant change in V(max) values during MP withd rawal, despite the presence of NE. The K(m) and V(max) values increase d when NE was the substrate. Inhibition of MAO by MP or its metabolite s (amphetamine, p-hydroxyamphetamine and p-hydroxymethamphetamine) inc reased with the use of the following substrates in the order: DA, 5-HT . NE and beta-PEA.