Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 407 East 61th Street, New York, NY 10065, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jul 2;38(1):21-9. doi: 10.1016/j.pnpbp.2011.12.004. Epub 2012 Jan 11.
Cannabinoid modulation of dopaminergic transmission is suggested by the ability of delta9-tetrahydrocanabinoid to affect motor and motivated behaviors in a manner similar to that produced by pharmacological manipulation of the nigrostriatal and mesocorticolimbic dopamine systems. These behavioral effects as well as analogous effects of endocannabinoids are largely mediated through the cannabinoid type 1 receptor (CB1R). This receptor is located within the substantia nigra and ventral tegmental area, which respectively house the somata of nigrostriatal and mesocorticolimbic dopaminergic neurons. The CB1R is also abundantly expressed in brain regions targeted by the efferent terminals of these dopaminergic neurons. In this review we present the accumulating anatomical and electrophysiological evidence indicating that in each of these systems cannabinoids modulate dopamine transmission largely if not exclusively through indirect mechanisms. The summarized mechanisms include presynaptic release of amino acid transmitters onto midbrain dopamine neurons and onto both cortical and striatal neurons that express dopamine D1-like or D2-like receptors functionally affiliated with the CB1 receptor. The review concludes with a consideration of the psychiatric and neurological implications of cannabinoid modulation of dopamine transmission within these networks.
大麻素对多巴胺能传递的调节作用是由 δ9-四氢大麻酚影响运动和动机行为的能力所提示的，其方式类似于对黑质纹状体和中脑边缘多巴胺系统的药理学操作产生的作用。这些行为效应以及内源性大麻素的类似效应主要通过大麻素 1 型受体 (CB1R) 介导。该受体位于黑质和腹侧被盖区，分别包含黑质纹状体和中脑边缘多巴胺能神经元的体细胞。CB1R 也在这些多巴胺能神经元的传出末端靶向的脑区中大量表达。在这篇综述中，我们提出了累积的解剖学和电生理学证据，表明在这些系统中的每一个系统中，大麻素对多巴胺传递的调节主要（如果不是完全的话）是通过间接机制实现的。总结的机制包括氨基酸递质对中脑多巴胺神经元的突触前释放，以及对表达与 CB1 受体功能相关的多巴胺 D1 样或 D2 样受体的皮质和纹状体神经元的释放。该综述最后考虑了大麻素对这些网络中多巴胺传递的调节对精神和神经的影响。
