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 evidence of dopaminergic and serotonergic neurotoxicity, there is evidence of MA-induced behavioral changes. In this regard, stereotypic behavior elicited by MA is greater in rats treated previously with a neurotoxic regimen of MA than in control animals. The present study was designed to determine whether the enhanced stereotypy observed in MA-treated rats is due to the MA-induced loss of dopamine (neurotoxicity) or to the repeated exposure to MA (sensitization). Rats were treated with MA (10 mg/kg every 2 h for four injections) or vehicle at either a normal (24 degrees C) room temperature or a cold (4 degrees C) room temperature, which has been shown to attenuate the MA-induced loss of dopamine. Stereotypy was assessed 7 days after treatment. Rats that had received a neurotoxic regimen of MA at 24 degrees C exhibited 49% and 45% reductions in neostriatal dopamine and serotonin concentrations, respectively, whereas rats treated with MA at 4 degrees C had no significant neurochemical depletions. Stereotypy elicited by MA (5.0 mg/kg) was significantly greater in rats treated with a neurotoxic regimen of MA regardless of the initial treatment temperature. In addition, an injection of apomorphine (0.5 mg/kg) elicited an enhanced stereotypic response in MA-treated rats. These data suggest that the augmented stereotypic behavior observed in rats treated with a neurotoxic regimen of MA is not due to the loss of dopamine, but rather the manifestation of behavioral sensitization, possibly due to an increase in dopamine receptor sensitivity.
(Copyright 2001 Wiley-Liss, Inc.)