Caillé Stéphanie, Parsons Loren H
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Neuropsychopharmacology. 2006 Apr;31(4):804-13. doi: 10.1038/sj.npp.1300848.
Recent evidence indicates that cannabinoid-1 (CB1) receptors play a role in the mediation of opiate reward, though the neural mechanisms for this process have not been characterized. The present experiments investigated the influence of CB1 receptors in the ventral striatopallidal system on opiate-induced neurochemical events and opiate self-administration behavior in rats. Acute morphine administration (3 mg/kg) significantly reduced ventral pallidal GABA efflux in a manner similar to that produced by heroin self-administration. This neurochemical effect was reversed by doses of the selective CB1 antagonist SR 141716A (Rimonabant; 1 and 3 mg/kg) that also significantly reduce opiate reward. Morphine-induced increases in nucleus accumbens dopamine levels were unaltered by SR 141716A. Intravenous heroin self-administration (0.02 mg/infusion) was significantly reduced by intra-accumbens, but not intraventral pallidal SR 141716A infusions (1 and 3 microg/side), implicating nucleus accumbens CB1 receptors in the modulation of opiate reinforcement. In contrast, SR14716A did not alter cocaine self-administration (0.125 mg/inf), cocaine-induced (10 mg/kg) decrements in ventral pallidal GABA efflux or cocaine-induced increases in accumbens dopamine. This is consistent with evidence that selective inactivation of CB1 receptors reduces opiate-, but not psychostimulant-maintained self-administration. The CB1 receptor agonist WIN 55,212-2 (5 mg/kg) reduced pallidal GABA efflux in a manner similar to morphine, and this effect was reversed by the opiate receptor antagonist naloxone. Collectively these findings suggest that CB1 receptors modulate opiate reward through the ventral striatopallidal projection and that the modulation of this projection system may be involved in the reciprocal behavioral effects between cannabinoids, and opioids.
最近的证据表明，大麻素-1（CB1）受体在阿片类药物奖赏的介导中发挥作用，尽管这一过程的神经机制尚未明确。本实验研究了腹侧纹状体苍白球系统中的CB1受体对大鼠阿片类药物诱导的神经化学事件及阿片类药物自我给药行为的影响。急性给予吗啡（3毫克/千克）以类似于海洛因自我给药产生的方式显著降低了腹侧苍白球的GABA外流。这种神经化学效应被选择性CB1拮抗剂SR 141716A（利莫那班；1和3毫克/千克）的剂量所逆转，该剂量也显著降低了阿片类药物奖赏。SR 141716A并未改变吗啡诱导的伏隔核多巴胺水平升高。静脉注射海洛因自我给药（0.02毫克/次）通过伏隔核内注射SR 141716A（1和3微克/侧）显著降低，但腹侧苍白球内注射则无此效果，这表明伏隔核CB1受体参与了阿片类药物强化作用的调节。相比之下，SR14716A并未改变可卡因自我给药（0.125毫克/次）、可卡因诱导的（10毫克/千克）腹侧苍白球GABA外流减少或可卡因诱导的伏隔核多巴胺增加。这与选择性灭活CB1受体可降低阿片类药物维持的自我给药，但不降低精神兴奋剂维持的自我给药的证据一致。CB1受体激动剂WIN 55,212-2（5毫克/千克）以类似于吗啡的方式降低了苍白球GABA外流，且这种效应被阿片受体拮抗剂纳洛酮所逆转。这些研究结果共同表明，CB1受体通过腹侧纹状体苍白球投射调节阿片类药物奖赏，并且该投射系统的调节可能参与了大麻素和阿片类药物之间的相互行为效应。
