Broening Harry W, Morford Laronda L, Vorhees Charles V
Division of Developmental Biology, Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Synapse. 2005 May;56(2):84-93. doi: 10.1002/syn.20130.
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 degrees C. Methamphetamine administered at 24 degrees 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 degrees C attenuated methamphetamine-induced hyperthermia and prevented significant reductions in dopamine content. At 33 degrees 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 degrees C eticlopride-methamphetamine group. Thus, although the eticlopride-methamphetamine treatment combination at 33 degrees C exhibited a hyperthermic response comparable to that seen with methamphetamine alone at 24 degrees C, reductions in dopamine content were attenuated in the combination group compared with methamphetamine alone at 24 degrees C. Serotonin changes showed similar attenuated reductions after SCH-23390 or eticlopride pretreatment at 24 degrees C in combination with methamphetamine, but this attenuation was absent at 33 degrees 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.
研究了多巴胺D1受体拮抗剂R(+)-SCH-23390和D2受体拮抗剂S(-)-艾替洛尔对治疗72小时后d-甲基苯丙胺诱导的纹状体单胺减少的影响，并与体温变化相关联。给大鼠注射四剂10mg/kg的d-甲基苯丙胺或生理盐水，每次注射间隔2小时；在每次注射甲基苯丙胺或生理盐水前15分钟给予0.5mg/kg的艾替洛尔或SCH-23390。研究了两种环境温度条件：24℃和33℃。在24℃下给予甲基苯丙胺会引起体温过高，并使纹状体多巴胺含量降低73%；在24℃下，与甲基苯丙胺联合给予0.5mg/kg的艾替洛尔或SCH-23390可减轻甲基苯丙胺诱导的体温过高，并防止多巴胺含量显著降低。在33℃时，艾替洛尔和SCH-23390在阻断甲基苯丙胺诱导的体温过高方面无效，在SCH-23390-甲基苯丙胺组中多巴胺含量降低了65%。相比之下，在33℃的艾替洛尔-甲基苯丙胺组中，多巴胺含量仅降低了31%。因此，尽管在33℃下艾替洛尔-甲基苯丙胺治疗组合表现出与在24℃下单独使用甲基苯丙胺时相当的体温过高反应，但与在24℃下单独使用甲基苯丙胺相比，联合组中多巴胺含量的降低有所减轻。在24℃下，与甲基苯丙胺联合使用时，SCH-23390或艾替洛尔预处理后血清素变化也显示出类似的减轻降低，但在33℃时这种减轻不存在。艾替洛尔预处理后观察到的甲基苯丙胺诱导的纹状体多巴胺减少与体温过高的分离表明，多巴胺D2受体机制介导了甲基苯丙胺诱导的多巴胺耗竭。然而，这种D2机制不适用于甲基苯丙胺诱导的纹状体血清素减少。
