Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia
Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia
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DOI：
10.1016/s0306-4522(03)00070-8
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Garcia-Segura, LM
中科院分区：
文献类型：
--
作者：
Julian, MD;Martin, AB;Garcia-Segura, LM
多巴胺和内源性大麻素是已知的神经递质，在基底节运动神经回路的活动中发挥作用。虽然许多研究已经证明了1型大麻素(CB1)受体和多巴胺能系统之间的功能相互作用，但我们仍然缺乏详细的神经解剖学证据来解释它们之间的关系。采用原位杂交和免疫组织化学方法检测CB1受体和酪氨酸羟化酶(TH)在基底节的表达和定位。在纹状体中，我们发现CB1受体转录本有强信号，但CB1受体蛋白有低信号，而在苍白球和黑质中，我们发现相反的信号；没有杂交信号，但有强烈的免疫反应。因此，CB1受体在纹状体合成，并主要运输到其靶区。未发现CB1受体和TH的共表达或共定位。在尾壳核、苍白球和黑质，TH免疫反应纤维与CB1受体免疫反应神经纤维和纤维相互交织。我们的数据表明，大多数纹状体CB1受体位于突触前抑制性GABA能终末，调节神经递质的释放，影响黑质多巴胺能神经元的活动。反过来，来自黑质的传入多巴胺能纤维支配表达CB1受体的纹状体神经元，已知的纹状体神经元也表达多巴胺受体。总之，这些数据为解释基底节内源性大麻素和多巴胺能系统之间的功能相互作用提供了神经解剖学基础。(C)2003年IBRO。爱思唯尔科学有限公司出版。版权所有。
Dopamine and endocannabinoids are neurotransmitters known to play a role in the activity of the basal ganglia motor circuit. While a number of studies have demonstrated functional interactions between type 1 cannabinoid (CB1) receptors and dopaminergic systems, we still lack detailed neuroanatomical evidence to explain their relationship. Single- and double-labeling methods (in situ hybridization and immunohistochemistry) were employed to determine both the expression and localization of CB1 receptors and tyrosine hydroxylase (TH) in the basal ganglia. In the striatum, we found an intense signal for CB1 receptor transcripts but low signal for CB1 receptor protein, whereas in the globus pallidus and substantia nigra we found the opposite; no hybridization signal but intense immunoreactivity. Consequently, CB1 receptors are synthesized in the striatum and mostly transported to its target areas. No co-expression or co-localization of CB1 receptors and TH was found. In the caudate-putamen, globus pallidus and substantia nigra, TH-immunoreactive fibers were interwoven with the CB1 receptor-immunoreactive neuropil and fibers. Our data suggest that the majority of the striatal CB1 receptors are located presynaptically on inhibitory GABAergic terminals, in a position to modulate neurotransmitter release and influence the activity of substantia nigra dopaminergic neurons. In turn, afferent dopaminergic fibers from the substantia nigra innervate CB1 receptor-expressing striatal neurons that are known to also express dopamine receptors. In conclusion, these data provide a neuroanatomical basis to explain functional interactions between endocannabinoid and dopaminergic systems in the basal ganglia. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.