Cannabinoid modulation of opiate reinforcement through the ventral striatopallidal pathway
Cannabinoid modulation of opiate reinforcement through the ventral striatopallidal pathway
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DOI：
10.1038/sj.npp.1300848
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发表时间：
2006-04-01
影响因子：
7.6
通讯作者：
Parsons, LH
中科院分区：
文献类型：
--
作者：
Caillé, S;Parsons, LH
最近的证据表明，大麻素-1（CB 1）受体在阿片奖赏的介导中发挥作用，尽管这一过程的神经机制尚未被表征。本实验研究了大鼠腹侧纹状体苍白球系统CB 1受体对阿片类药物诱发的神经化学事件和阿片类药物自我给药行为的影响。急性吗啡给药（3毫克/公斤）显着减少腹侧苍白球GABA流出的方式类似于海洛因自我管理。这种神经化学作用被选择性CB 1拮抗剂SR 141716 A（利莫那班; 1和3 mg/kg）逆转，也显著降低阿片类药物的奖励。SR 141716 A没有改变吗啡诱导的伏隔核多巴胺水平增加。静脉注射海洛因自我管理（0.02毫克/输注）显着减少了intraperebens，但不intraventral苍白球SR 141716 A输注（1和3微克/侧），牵连核CB 1受体的阿片类药物强化的调制。相比之下，SR 14716 A未改变可卡因自我给药（0.125 mg/inf）、可卡因诱导（10 mg/kg）的腹侧苍白球GABA流出减少或可卡因诱导的多巴胺增加。这与CB 1受体的选择性失活减少阿片类药物而不是精神兴奋剂维持的自我给药的证据一致。CB 1受体激动剂WIN 55，212 -2（5 mg/kg）以类似于吗啡的方式减少苍白球GABA流出，阿片受体拮抗剂纳洛酮可逆转该作用。总的来说，这些研究结果表明，CB 1受体调节阿片类药物的奖励通过腹侧striatopallidal的投影和调制这个投影系统可能参与大麻素和阿片类药物之间的相互行为效应。
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 mu g/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.