大麻素CB1受体拮抗剂AM251不会改变甲基苯丙胺诱导的反应恢复。
The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding.
作者信息
Boctor Sherin Y, Martinez Joe L, Koek Wouter, France Charles P
机构信息
Cajal Neuroscience Institute, Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
出版信息
Eur J Pharmacol. 2007 Sep 24;571(1):39-43. doi: 10.1016/j.ejphar.2007.06.004. Epub 2007 Jun 13.
Cannabinoid CB(1) receptor antagonists can decrease methamphetamine self-administration. This study examined whether the CB(1) receptor antagonist AM251 [N-(piperidin-1-yl)-5-(4-indophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] modifies reinstatement in rats that previously self-administered methamphetamine. Rats (n=10) self-administered methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 2 schedule. Non-contingent methamphetamine (0.01-1.78 mg/kg, i.v.) yielded responding for saline (reinstatement) that was similar to responding for self-administered methamphetamine. AM251 (0.032-0.32, i.v.) did not affect methamphetamine-induced reinstatement but significantly attenuated Delta(9)-tetrahydrocannabinol (2.0 mg/kg, i.p.)-induced hypothermia. These data fail to support a role for endogenous cannabinoids or cannabinoid CB(1) receptors in reinstatement and, therefore, relapse to stimulant abuse.
大麻素CB(1)受体拮抗剂可减少甲基苯丙胺的自我给药行为。本研究考察了CB(1)受体拮抗剂AM251 [N-(哌啶-1-基)-5-(4-吲哚苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺]对先前自我给药甲基苯丙胺的大鼠复吸行为的影响。大鼠（n=10）在固定比率2的条件下自我给药甲基苯丙胺（0.1 mg/kg/次注射）。非条件性甲基苯丙胺（0.01 - 1.78 mg/kg，静脉注射）引发对生理盐水的反应（复吸），这与对自我给药甲基苯丙胺的反应相似。AM251（0.032 - 0.32，静脉注射）不影响甲基苯丙胺诱导的复吸，但显著减弱了Δ(9)-四氢大麻酚（2.0 mg/kg，腹腔注射）诱导产生的体温过低。这些数据不支持内源性大麻素或大麻素CB(1)受体在复吸以及因此在兴奋剂滥用复发中起作用。
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