Dopamine activation of endogenous cannabinoid signaling in dorsal striatum
Dopamine activation of endogenous cannabinoid signaling in dorsal striatum
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DOI：
10.1038/7268
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发表时间：
1999-04-01
影响因子：
25
通讯作者：
Piomelli, D
中科院分区：
文献类型：
--
作者：
Giuffrida, A;Parsons, LH;Piomelli, D
用微渗析和气相色谱-质谱法测定了自由活动大鼠背侧纹状体内源性大麻素的释放。神经活动刺激了内源性大麻素的释放，但不能刺激其他内源性大麻素的释放，如2-花生四烯基甘油。此外，局部给药D-2-样(D-2，D-3，D-4)多巴胺受体激动剂奎匹罗后，阿南达胺的释放量比基线增加8倍，这一反应可被D-2样受体拮抗剂雷氯普利阻止。给予类D-1(D-1，D-5)受体激动剂SKF38393则无此作用。这些结果表明，内源性大麻素和多巴胺能系统之间的功能相互作用可能有助于纹状体信号的传递。与这一假设一致的是，大麻素拮抗剂SR141716A的预处理增强了全身给药奎比罗对运动行为的刺激。因此，内源性大麻素系统可能起到抑制反馈机制的作用，对抗多巴胺诱导的运动活动的促进。
We measured endogenous cannabinoid release in dorsal striatum of freely moving rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release was increased eightfold over baseline after local administration of the D-2-like (D-2, D-3, D-4) dopamine receptor agonist quinpirole, a response that was prevented by the D-2-like receptor antagonist raclopride. Administration of the D-1-like (D-1, D-5) receptor agonist SKF38393 had no such effect. These results suggest that functional interactions between endocannabinoid and dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716A enhanced the stimulation of motor behavior elicited by systemic administration of quinpirole. The endocannabinoid system therefore may act as an inhibitory feedback mechanism countering dopamine-induced facilitation of motor activity.