Competitive and noncompetitive N-methyl-D-aspartate antagonists protect dopaminergic and serotonergic neurotoxicity...

Protective effects of NMDA antagonists on dopaminergic and serotonergic neurotoxicity produced by methamphetamine (MA) were examined. Four injections of MA (7.5 mg/kg, s.c., at 2 h intervals) caused significant decrements (40-60% of control values) in levels of dopamine (DA) and its metabolites in the rat striatum and levels of serotonin (5-HT) and its metabolite in the medial prefrontal cortex, nucleus accumbens, striatum, anterior hypothalamus, amygdala and hippocampus. These decreases in DA, 5-HT and their metabolites were prevented by pretreatment with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, or D-CPP-ene (SDZ EAA 494), a competitive NMDA antagonist. The results suggest that NMDA receptors play a role for MA-induced serotonergic damage in various brain regions as well as dopaminergic damage in the striatum.