Hatzipetros Theo, Yamamoto Bryan K
Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA
Brain Res. 2006 Mar 3;1076(1):60-7. doi: 10.1016/j.brainres.2006.01.015.
The regulation of the glutamatergic projection from the subthalamic nucleus (STN) to the substantia nigra (SN) was investigated using dual-probe microdialysis in the awake behaving rat. Reverse dialysis of the cholinergic receptor agonist carbachol (1 mM) into the STN caused an increase in the extracellular concentrations of glutamate and dopamine in the SN. The increase in glutamate was transient and returned toward basal values despite the continued perfusions of the STN with carbachol. Carbachol-stimulated glutamate release was prolonged by perfusion of the selective D2 dopamine receptor antagonist raclopride (100 microM) into the SN and was attenuated by the perfusion of the selective D2-like receptor agonist quinpirole (10 microM). In contrast, perfusion of the D1 dopamine receptor antagonist SCH-23390 (100 microM) did not alter the carbachol-stimulated glutamate release even though it increased basal glutamate concentrations. Perfusion of the GABAA receptor antagonist bicuculline (10 microM) into the SN prolonged the carbachol-stimulated glutamate release in similar fashion as raclopride. The present findings suggest that somatodendritically released dopamine in the SN regulates glutamate release from subthalamic axon terminals by differentially activating dopamine D2 and D1 receptors. Activation of D2 heteroreceptors, located on STN axon terminals, provides a negative feedback control on stimulated subthalamic glutamate release, while D1 receptor activation preferentially regulates basal glutamate concentrations. The findings of the present study also indicate that GABA exerts an inhibitory control on glutamate release in the SN through GABAA receptors.
利用双探针微透析技术，在清醒行为大鼠中研究了从丘脑底核（STN）到黑质（SN）的谷氨酸能投射的调节。将胆碱能受体激动剂卡巴胆碱（1 mM）逆向透析到STN中，导致SN中谷氨酸和多巴胺的细胞外浓度增加。尽管继续向STN灌注卡巴胆碱，但谷氨酸的增加是短暂的，并恢复到基础值。将选择性D2多巴胺受体拮抗剂雷氯必利（100 μM）灌注到SN中可延长卡巴胆碱刺激的谷氨酸释放，而将选择性D2样受体激动剂喹吡罗（10 μM）灌注到SN中则可减弱这种释放。相比之下，灌注D1多巴胺受体拮抗剂SCH-23390（100 μM）尽管会增加基础谷氨酸浓度，但并未改变卡巴胆碱刺激的谷氨酸释放。将GABAA受体拮抗剂荷包牡丹碱（10 μM）灌注到SN中，以与雷氯必利类似的方式延长了卡巴胆碱刺激的谷氨酸释放。目前的研究结果表明，SN中树突体释放的多巴胺通过差异性激活多巴胺D2和D1受体来调节丘脑底轴突终末的谷氨酸释放。位于STN轴突终末的D2异受体的激活，对刺激的丘脑底谷氨酸释放提供负反馈控制，而D1受体激活则优先调节基础谷氨酸浓度。本研究的结果还表明，GABA通过GABAA受体对SN中的谷氨酸释放发挥抑制性控制。
