Mesolimbic dopaminergic decline after cannabinoid withdrawal
Mesolimbic dopaminergic decline after cannabinoid withdrawal
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DOI：
10.1073/pnas.95.17.10269
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发表时间：
1998-08-18
影响因子：
11.1
通讯作者：
Gessa, GL
中科院分区：
文献类型：
--
作者：
Diana, M;Melis, M;Gessa, GL
中脑边缘多巴胺系统最近被认为与戒断主要滥用药物的长期不良后果有关。在目前的研究中，我们试图确定中脑边缘多巴胺神经元是否参与了慢性大麻类药物戒断的神经生物学机制。用大麻和大麻的主要精神活性成分Delta(9)-四氢大麻酚(Delta(9)-THC)长期治疗大鼠。给予大麻素拮抗剂SR 141716A可引起强烈的行为戒断综合症，而突然的Delta(9)-THC混悬液未能产生明显的戒断迹象。相反，两组都表现出多巴胺细胞活性的降低，从逆行鉴定的Mesoavbens多巴胺神经元的细胞外单个单位记录中可以看出。给自发戒断的大鼠注射Delta(9)-THC恢复了神经元的活动。相反，SR 141716A在大麻素处理组的自发活动进一步减少，尽管它对对照组大鼠无效。这些数据表明，与其他成瘾药物相似，停止长期服用大麻素与边缘系统多巴胺能传递减少有关；这些神经元可塑性的变化可能在药物渴望和复发成瘾中发挥作用。
The mesolimbic dopamine system has recently been implicated in the long-term aversive consequences of withdrawal from major drugs of abuse. In the present study we sought to determine whether mesolimbic dopamine neurons are involved in the neurobiologic mechanisms underlying withdrawal from chronic cannabinoid exposure. Rats were treated chronically with the major psychoactive ingredient of hashish and marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Administration of the cannabinoid antagonist SR 141716A precipitated an intense behavioral withdrawal syndrome, whereas abrupt Delta(9)-THC suspension failed to produce overt signs of abstinence. In contrast, both groups showed a reduction in dopamine cells activity as indicated by extracellular single unit recordings from antidromically identified mesoaccumbens dopamine neurons. The administration of Delta(9)-THC to spontaneously withdrawn rats restored neuronal activity. Conversely, SR 141716A produced a further decrease of spontaneous activity in cannabinoid-treated although it was ineffective in control rats. These data indicate that withdrawal from chronic cannabinoid administration is associated with reduced dopaminergic transmission in the limbic system, similar to that observed with other addictive drugs; these changes in neuronal plasticity may play a role in drug craving and relapse into drug addiction.