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.
Wallace
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TL
Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio, USA.
Gudelsky
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GA
Vorhees
C V
CV
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003080:Cold Temperature / Q000009:adverse effects; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
D009498:Neurotoxins; D011954:Receptors, Dopamine; D012701:Serotonin; D008694:Methamphetamine; D001058:Apomorphine; D004298:Dopamine