PRETREATMENT WITH ASCORBIC-ACID ATTENUATES THE NEUROTOXIC EFFECTS OF METHAMPHETAMINE IN RATS

Abstract

The toxic effects of methamphetamine on dopamine and serotonergic neurons is linked to the endogenous formation of 6-hydroxydopamine and 5,7-dihydroxytryptamine, respectively. The ability of methamphetamine of both release dopamine and serotonin [5-hydroxytryptamine, 5-HT] as well as to inhibit monoamine oxidase activity may lead to the non-enzymatic oxidation of dopamine and 5-HT to the neurotoxins. Rats were pretreated with high doses of an antioxidant (ascorbic acid) prior to the administration of methamphetamine. The administration of 25.0 mg/kg of methamphetamine at 12 h intervals for a 4 day period caused a long-lasting depletion of dopamine and 5-HT. Pretreatment with 100.0 mg/kg of ascorbic acid 30 min 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.