Neurotoxic regimen of methamphetamine produces evidence of behavioral sensitization in the rat

A neurotoxic regimen of methamphetamine (MA) produces long-term depletions in neostriatal dopamine and serotonin concentrations. In addition to eviden ce of dopaminergic and serotonergic neurotoxicity, there is evidence of MA- induced behavioral changes. In this regard, stereotypic behavior elicited b y MA is greater in rats treated previously with a neurotoxic regimen of MA than in control animals. The present study was designed to determine whethe r the enhanced stereotypy observed in MA-treated rats is due to the MA-indu ced loss of dopamine (neurotoxicity) or to the repeated exposure to MA (sen sitization). Rats were treated with MA (10 mg/kg every 2 h for four injecti ons) or vehicle at either a normal(24 degreesC) room temperature or a cold (4 degreesC) room temperature, which has been shown to attenuate the MA-ind uced loss of dopamine. Stereotypy was assessed 7 days after treatment. Rats that had received a neurotoxic regimen of MA at 24 degreesC exhibited 49% and 45% reductions in neostriatal dopamine and serotonin concentrations, re spectively, whereas rats treated with MA at 4 degreesC had no significant n eurochemical depletions. Stereotypy elicited by MA (5.0 mg/kg) was signific antly greater in rats treated with a neurotoxic regimen of MA regardless of the initial treatment temperature. In addition, an injection of apomorphin e (0.5 mg/kg) elicited an enhanced stereotypic response in MA-treated rats. These data suggest that the augmented stereotypic behavior observed in rat s treated with a neurotoxic regimen of MA is not due to the loss of dopamin e, but rather the manifestation of behavioral sensitization, possibly due t o an increase in dopamine receptor sensitivity. (C) 2001 Wiley-Liss, Inc.