Methamphetamine-induced dopaminergic toxicity in mice. Role of environmental temperature and pharmacological agents
Abstract
1. Multiple injections of METH (4 x 10 mg/kg, i.p.) at room temperature (23 degrees C) produced a significant depletion of dopamine (DA) and its metabolites DOPAC and HVA in striatum at 24 and 72 hr, and 1 and 2 wk. 2. Three days post 4 x 10 mg/kg METH at 23 degrees C, an 80% decrease in striatal dopamine (DA) occurred, while the same dose at 4 degrees C produced only a 20% DA decrease, and 4 x 20 mg/kg METH at 4 degrees C produced a 54% DA decrease. A similar pattern in the decreases of the DA metabolites DOPAC and HVA was observed after METH administration. 3. At 23 degrees C (+)MK-801 completely blocked while phenobarbital (40% decrease) and diazepam (65% decrease) partially blocked decreases in striatal DA produced by 4 x 10 mg/kg METH. Decreases in DOPAC and HVA were similar to the decreases in DA after METH and antagonists. 4. Multiple injections of METH (4 x 10 mg/kg, i.p.) at room temperature also produced a significant depletion of serotonin (5-HT) in striatum at 24 and 72 hr, and 1 and 2 wk. The depletion of 5-HT metabolite 5-HIAA was found only at 72 hr post-dosing. 5. This depletion of 5-HT and its metabolite 5-HIAA at room temperature was blocked either by changing the environmental temperature to 4 degrees C, or b...Continue Reading
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