OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA
OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA
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DOI：
10.1111/j.1440-1681.1995.tb01947.x
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发表时间：
1995-11-01
影响因子：
2.9
通讯作者：
WILLIAMS, JT
中科院分区：
文献类型：
--
作者：
CAMERON, DL;WILLIAMS, JT
1、多巴胺D-1和5HT（1D）受体位于传入GABA神经元的末端，该神经元与腹侧被盖区（VTA）多巴胺神经元突触。利用细胞内记录的方法研究了这些受体在可卡因作用中的作用，在脑切片中产生突触电位，并鉴定了gaba介导的抑制性突触后电位（IPSP）。多巴胺D-1受体的刺激选择性地增强了GABAB的IPSP，而这种作用被D-1拮抗剂阻断，当D-1拮抗剂单独应用时，IPSP的强度降低，提示通过树突释放多巴胺刺激D-1受体。可卡因有相反的作用，选择性地降低GABAB IPSP的大小。这种作用被5HT和5HT（1D）激动剂舒马匹坦模拟，并被5HT（1D/2C）拮抗剂美高林减弱。5ht释放剂芬氟拉明也能模仿可卡因的作用，并通过将切片与5ht消耗剂对氯苯丙胺预先孵化而阻断。本研究结果表明，多巴胺和5HT在调节GABA输入VTA多巴胺神经元中具有相反的作用，可卡因在这种相互作用中的作用可能有助于理解其成瘾特性。
1, Dopamine D-1 and 5HT(1D) receptors are found on the terminals of afferent GABA neurons that synapse on the ventral tegmental area (VTA) dopamine neurons. The role of these receptors in the actions of cocaine was investigated using intracellular recordings in a brain slice preparation, Synaptic potentials were generated in the slice and GABA-mediated inhibitory post-synaptic potentials (IPSP) were identified.2. Stimulation of dopamine D-1 receptors selectively enhanced the GABAB IPSP, and this effect was blocked by D-1 antagonists, The magnitude of the IPSP was decreased when D-1 antagonists were applied in isolation, suggesting tonic D-1 receptor stimulation via dendritically released dopamine.3. Cocaine had an opposite effect and selectively decreased the magnitude of the GABAB IPSP. This action was mimicked by 5HT and the 5HT(1D) agonist sumatriptan, and attenuated by the 5HT(1D/2C) antagonist, metergoline. The action of cocaine was also mimicked by the 5HT-releasing agent, fenfluramine, and blocked by pre-incubation of the slice with the 5HT-depleting agent, para-chloroamphetamine.4. The results of this study suggest that dopamine and 5HT have opposing roles in modulating GABA input into VTA dopamine neurons, The actions of cocaine on this interplay may have implications for understanding its addictive properties.