Herkenham M, Lynn A B, de Costa B R, Richfield E K
Section on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892.
Brain Res. 1991 May 3;547(2):267-74. doi: 10.1016/0006-8993(91)90970-7.
Cannabinoid receptors have recently been characterized and localized using a high-affinity radiolabeled cannabinoid analog in section binding assays. In rat brain, the highest receptor densities are in the globus pallidus and substantia nigra pars reticulata. Receptors are also dense in the caudate-putamen. In order to determine the neuronal localization of these receptors, selective lesions of key striatal afferent and efferent systems were made. Striatal neurons and efferent projections were selectively destroyed by unilateral infusion of ibotenic acid into the caudate-putamen. The nigrostriatal pathway was selectively destroyed in another set of animals by infusion of 6-hydroxydopamine into the medial forebrain bundle. After 2- or 4-week survivals, slide-mounted brain sections were incubated with ligands selective for cannabinoid ([3H]CP 55,940), dopamine D1 3H]SCH-23390) and D2 ([3H]raclopride) receptors, and dopamine uptake sites ([3H]GBR-12935). Slides were exposed to 3H-sensitive film. The resulting autoradiography showed ibotenate-induced losses of cannabinoid, D1 and D2 receptors in the caudate-putamen and topographic losses of cannabinoid and D1 receptors in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata at both survivals. Four weeks after medial forebrain bundle lesions (which resulted in amphetamine-induced rotations), there was loss of dopamine uptake sites in the striatum and substantia nigra pars compacta but no change in cannabinoid receptor binding. The data show that cannabinoid receptors in the basal ganglia are neuronally located on striatal projection neurons, including their axons and terminals. Cannabinoid receptors may be co-localized with D1 receptors on striatonigral neurons. Cannabinoid receptors are not localized on dopaminergic nigrostriatal cell bodies or terminals.
最近，在切片结合试验中使用高亲和力放射性标记的大麻素类似物对大麻素受体进行了表征和定位。在大鼠脑中，受体密度最高的区域是苍白球和黑质网状部。尾状核 - 壳核中的受体也很密集。为了确定这些受体的神经元定位，对关键的纹状体传入和传出系统进行了选择性损伤。通过向尾状核 - 壳核单侧注入鹅膏蕈氨酸选择性破坏纹状体神经元和传出投射。在另一组动物中，通过向内侧前脑束注入6 - 羟基多巴胺选择性破坏黑质纹状体通路。在存活2周或4周后，将脑切片置于载玻片上，与对大麻素（[3H]CP 55,940）、多巴胺D1（[3H]SCH - 23390）和D2（[3H]雷氯必利）受体以及多巴胺摄取位点（[3H]GBR - 12935）具有选择性的配体一起孵育。将载玻片暴露于3H敏感胶片。所得的放射自显影显示，在两个存活时间点，鹅膏蕈氨酸诱导尾状核 - 壳核中大麻素、D1和D2受体的损失，以及苍白球、内苍白球核和黑质网状部中大麻素和D1受体的拓扑学损失。在内侧前脑束损伤4周后（这导致苯丙胺诱导的旋转），纹状体和黑质致密部中的多巴胺摄取位点减少，但大麻素受体结合没有变化。数据表明，基底神经节中的大麻素受体在神经元上位于纹状体投射神经元上，包括它们的轴突和终末。大麻素受体可能与纹状体黑质神经元上的D1受体共定位。大麻素受体不在多巴胺能黑质纹状体细胞体或终末上定位。
