Dopamine prevents muscarinic-induced decrease of glutamate release in the auditory cortex
Dopamine prevents muscarinic-induced decrease of glutamate release in the auditory cortex
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DOI：
10.1016/j.neuroscience.2005.05.005
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Paz, RD
中科院分区：
文献类型：
--
作者：
Atzori, M;Kanold, PO;Paz, RD
乙酰胆碱和多巴胺在出现新的刺激时同时在皮层释放。除了一系列兴奋作用外，乙酰胆碱还减少作用于突触前毒蕈碱受体的谷氨酸的释放。通过记录听觉皮层II/III层神经元的兴奋性突触后电流，我们发现在没有多巴胺(20 μ M多巴胺中A（oxo)/A(ctr)=0.89 +/- 0.12）的情况下，氧tremorine对毒碱受体的激活降低了谷氨酸能电流的振幅(A(oxo)/A(ctr)= 0.53 +/- 17)，而没有多巴胺(A（oxo)/A(ctr)=0.89 +/- 0.12）。这些数据表明，对多巴胺的过度敏感性，如精神分裂症的假设，可以阻止与胆碱能皮质核激活相关的谷氨酸释放的减少。因此，抗精神病药物的作用机制可能是通过抑制听觉皮层的谷氨酸能信号。我们测试了氟哌啶醇、氯氮平和拉莫三嗪对谷氨酸突触电流及其毒蕈碱调节的影响。我们发现抗精神病药物不仅可以作为多巴胺受体拮抗剂重建毒蕈碱调节，而且可以直接抑制谷氨酸电流。这些结果表明突触前谷氨酸释放的调节可以解释抗精神病药物的双重作用途径。(c) 2005 IBRO。Elsevier Ltd.出版。版权所有。
Acetylcholine and dopamine are simultaneously released in the cortex at the occurrence of novel stimuli. In addition to a series of excitatory effects, acetylcholine decreases the release of glutamate acting on presynaptic muscarinic receptors. By recording evoked excitatory postsynaptic currents in layers II/III neurons of the auditory cortex, we found that activation of muscarinic receptors by oxotremorine reduces the amplitude of glutamatergic current (A(oxo/) A(ctr)=0.53 +/- 17) in the absence but not in the presence of dopamine (A(oxo)/A(ctr)=0.89 +/- 0.12 in 20 mu M dopamine). These data suggested that an excessive sensitivity to dopamine, such as postulated in schizophrenia, could prevent the decrease of glutamate release associated with the activation of cholinergic corticopetal nuclei. Thus, a possible mechanism of action of antipsychotic drugs could be through a depression of the glutamatergic signal in the auditory cortex. We tested the capability of haloperidol, clozapine and lamotrigine to affect glutamatergic synaptic currents and their muscarinic modulation. We found that antipsychotics not only work as dopamine receptor antagonists in re-establishing muscarinic modulation, but also directly depress glutamatergic currents. These results suggest that presynaptic modulation of glutamate release can account for a dual route of action of antipsychotic drugs. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.