组胺H(3)受体激活对甲基苯丙胺和可卡因在小鼠和松鼠猴体内行为兴奋作用的影响。
Effects of histamine H(3) receptor activation on the behavioral-stimulant effects of methamphetamine and cocaine in mice and squirrel monkeys.
作者信息
Banks Matthew L, Manvich Daniel F, Bauzo Rayna M, Howell Leonard L
机构信息
Yerkes National Primate Research Center , Emory University, Atlanta, GA 30329, USA.
出版信息
Pharmacology. 2009;83(3):164-9. doi: 10.1159/000191473. Epub 2009 Jan 15.
BACKGROUND
Cocaine and methamphetamine (METH) are two commonly abused drugs that have behavioral-stimulant properties. These stimulant effects are partially mediated by the dopaminergic system. Recent evidence has suggested that the histamine H(3) receptor (H(3)R) may modulate the release of dopamine induced by METH. The aim of the present study was to examine the role of H(3)R in the behavioral-stimulant effects of cocaine and METH in mice and monkeys.
METHODS
Nonhabituated, experimentally naïve mice (n = 5-6) were pretreated with the H(3)R agonist imetit 30 min before METH or cocaine, and activity was measured for 90 min. The behavioral-stimulant effects of METH and cocaine were also studied in squirrel monkeys (n = 3) under a fixed-interval schedule of stimulus termination. Monkeys were pretreated with imetit 30 min before the peak behavioral-stimulant doses of METH or cocaine derived from individual subjects.
RESULTS
Pretreatment with imetit did not affect basal activity in mice. Imetit significantly attenuated the behavioral-stimulant effects of METH, but not cocaine. In monkeys, no dose of imetit tested significantly altered the behavioral-stimulant effects of METH or cocaine.
CONCLUSION
These results suggest a role of H(3)R in the behavioral-stimulant effects of METH, but not cocaine, in mice and no role in monkeys.
背景
可卡因和甲基苯丙胺（冰毒）是两种常见的具有行为兴奋特性的滥用药物。这些兴奋作用部分由多巴胺能系统介导。最近有证据表明，组胺H(3)受体（H(3)R）可能调节冰毒诱导的多巴胺释放。本研究的目的是探讨H(3)R在可卡因和冰毒对小鼠和猴子行为兴奋作用中的作用。
方法
对未习惯、未经实验的小鼠（n = 5 - 6）在给予冰毒或可卡因前30分钟用H(3)R激动剂碘替丁预处理，然后测量90分钟内的活动情况。还在松鼠猴（n = 3）中按照固定间隔刺激终止时间表研究了冰毒和可卡因的行为兴奋作用。在从个体受试者得出的冰毒或可卡因行为兴奋峰值剂量前30分钟，用碘替丁对猴子进行预处理。
结果
碘替丁预处理不影响小鼠的基础活动。碘替丁显著减弱了冰毒的行为兴奋作用，但对可卡因没有影响。在猴子中测试的任何剂量的碘替丁都没有显著改变冰毒或可卡因的行为兴奋作用。
结论
这些结果表明，H(3)R在小鼠冰毒行为兴奋作用中起作用，但在可卡因行为兴奋作用中不起作用，在猴子中则不起作用。
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