Cocaine and amphetamine depress striatal GABAergic synaptic transmission through D2 dopamine receptors
Cocaine and amphetamine depress striatal GABAergic synaptic transmission through D2 dopamine receptors
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DOI：
10.1016/s0893-133x(01)00299-8
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发表时间：
2002-02-01
影响因子：
7.6
通讯作者：
Calabresi, P
中科院分区：
文献类型：
--
作者：
Centonze, D;Picconi, B;Calabresi, P
条纹是与滥用药物的药理作用有关的大脑区域。为了测试可卡因和安非他明可能参与该核突触传递的调节，我们将纹状体棘神经元的全细胞膜片钳记录与谷氨酸能或 GABA 能神经末梢的局灶刺激结合起来。我们发现可卡因 (1-600 AM) 和安非他明 (0.3-300 AM) 均未显着影响从这些细胞记录的谷氨酸介导的 EPSC。相反，两种药物均以剂量依赖性方式抑制 GABA 介导的 IPSC。这种作用是通过刺激多巴胺 (DA) D2 受体介导的，因为它可以被 3AM L-舒必利（一种 DA D2 样受体拮抗剂）阻止，而 DA D2 样受体激动剂喹吡罗 (0.3-30 AM) 可以模拟这种作用，并且在缺乏 DA D2 受体的小鼠中不存在。突触前机制 Ems 可能参与了这一作用，因为可卡因和安非他明都通过增加配对脉冲促进来抑制 GABA 能传递。可卡因和安非他明在 6-OHDA 诱导的黑质损伤后未能影响 GABA 能 IPSC，表明这两种药物通过释放内源性 DA 发挥作用。纹状体中 GABA 能突触传递的调节可能是精神兴奋剂对哺乳动物产生某些运动和认知作用的基础。
The striation is a brain area implicated in the pharmacological action of drugs of abuse. To test the possible involv,ement of both cocaine and amphetamine in the modulation of synaptic transmission in this nucleus, we coupled whole-cell patch clamp recordings from striatal spiny neurons to the focal stimulation of glutamatergic or GABAergic nerve terminals. We found that neither cocaine (1-600 AM) nor amphetamine (0.3-300 AM) significantly affected the glutamate-mediated EPSCs recorded from these cells. Conversely, both pharmacological agents depressed GABA-mediated IPSCs in a dose-dependent manner. This effect was mediated by the stimulation of dopamine (DA) D2 receptors since it was prevented by 3 AM L-sulpiride (a DA D2-like receptor antagonist), mimicked by the DA D2-like receptor agonist quinpirole (0.3-30 AM), and absent in mice lacking DA D2 receptors. A presynaptic mechanism Ems likely involved in this action since both cocaine and amphetamine depress GABAergic transmission by increasing paired-pulse facilitation. Cocaine and amphetamine failed to affect GABAergic IPSCs after 6-OHDA-induced nigral lesion, indicating that both drugs cause their effects through the release of endogenous DA. The modulation of GABAergic synaptic transmission in the striatum might underlie some motor and cognitive effects of psychostimulants in mammalians.