Effects of Intracerebroventricular Administration of 5-(Glutathion-S-yl)-α-methyldopamine on Brain Dopamine, Serotonin, and Norepinephrine Concentrations in Male Sprague-Dawley Rats
Chemical Research in Toxicology January 1, 1996 R. Timothy Miller, Serrine S. Lau, Terrence J. Monks 63 citations
The metabolite 5-(glutathion-S-yl)-alpha-methyldopamine, formed from the oxidation of alpha-methyldopamine in the presence of glutathione, reproduces several acute behavioral and neurochemical effects of the serotonergic neurotoxicants MDA and MDMA in rats. Intracerebroventricular injection of this conjugate caused hyperactivity, aggression, forepaw treading, and Straub tail—behaviors typical of serotonin release. It also produced short-term changes in dopaminergic, serotonergic, and noradrenergic systems, including increased dopamine synthesis and acute serotonin turnover, as well as depletion of brain norepinephrine similar to MDA's pressor effect. However, a single injection did not cause long-term serotonergic toxicity, suggesting that while acute dopamine turnover may be necessary for such toxicity, it is not sufficient on its own.