| Autor: |
Broening, Harry W., Morford, Laronda L., Vorhees, Charles V. |
| Zdroj: |
Synapse; May2005, Vol. 56 Issue 2, p84-93, 10p |
| Abstrakt: |
The effects of the dopamine D1 receptor antagonist R(+)-SCH-23390 and D2 receptor antagonist S(-)-eticlopride on d-methamphetamine-induced striatal monoamine reductions 72 h after treatment were investigated in relation to changes in body temperature. Rats were administered four 10-mg/kg doses of d-methamphetamine or saline with a 2-h interval between treatments; 0.5 mg/kg eticlopride or SCH-23390 was administered 15 min before each methamphetamine or saline injection. Two ambient temperature conditions were investigated: 24 and 33°C. Methamphetamine administered at 24°C induced hyperthermia and reduced striatal dopamine content by 73%; 0.5 mg/kg eticlopride or SCH-23390 administered in combination with methamphetamine at 24°C attenuated methamphetamine-induced hyperthermia and prevented significant reductions in dopamine content. At 33°C, eticlopride and SCH-23390 were ineffective in blocking methamphetamine-induced hyperthermia and dopamine content was reduced by 65% in the SCH-23390-methamphetamine group. By contrast, dopamine content was reduced by only 31% in the 33°C eticlopride-methamphetamine group. Thus, although the eticlopride-methamphetamine treatment combination at 33°C exhibited a hyperthermic response comparable to that seen with methamphetamine alone at 24°C, reductions in dopamine content were attenuated in the combination group compared with methamphetamine alone at 24°C. Serotonin changes showed similar attenuated reductions after SCH-23390 or eticlopride pretreatment at 24°C in combination with methamphetamine, but this attenuation was absent at 33°C. The dissociation of methamphetamine-induced striatal dopamine reduction and hyperthermia seen after eticlopride pretreatment suggests a dopamine D2 receptor mechanism in mediating methamphetamine-induced dopamine depletion. However this D2 mechanism does not apply to methamphetamine-induced striatal serotonin reductions. Synapse 56:84-93, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR] |
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