Pretreatment with ascorbic acid attenuates the neurotoxic effects of methamphetamine in rats

The toxic effects of methamphetamine on dopamine and serotonergic neurons have recently been linked to the endogenous formation of 6-hydroxydopamine and 5,7-dihydroxytryptamine, respectively. It has been speculated that the ability of methamphetamine to both release dopamine and serotonin as well as to inhibit monoamine oxidase activity leads to the non-enzymatic oxidation of dopamine and serotonin to the neurotoxins. This hypothesis was evaluated by pretreating rats with high doses of an antioxidant (ascorbic acid) prior to the administration of methamphetamine. It was observed that the administration of 25.0 mg/kg of methamphetamine at 12 hour intervals for a four day period caused a long-lasting depletion of dopamine and serotonin. Pretreatment with 100.0 mg/kg of ascorbic acid 30 minutes before each methamphetamine injection significantly (but not completely) attenuated this neurotoxic action of methamphetamine. These observations are discussed in reference to animal models of Parkinson's disease.