Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex
Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex
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DOI：
10.1093/cercor/bhg128
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发表时间：
2004-03-01
期刊：
影响因子：
3.7
通讯作者：
Artigas, F
中科院分区：
文献类型：
--
作者：
Amargós-Bosch, M;Bortolozzi, A;Artigas, F
前额叶皮层在控制高级脑功能中起着关键作用，并参与精神分裂症的病理生理学和治疗。在此，我们报道了大鼠和小鼠前额叶皮质中大约60%的神经元表达5-HT 1A和/或5-HT 2A受体mRNA，它们高度共定位（大约80%）。电刺激中缝背核和中缝正中核引起5-HT 1A介导的抑制和5-HT 2A介导的兴奋在确定的锥体神经元细胞外记录在大鼠内侧前额叶皮层（mPFC）。在不同的坐标刺激中缝核可在同一锥体神经元内引起相反的反应，提示锥体神经元内5-HT神经元亚群与5-HT 1A和5-HT 2A受体之间存在精确的连接。微透析实验表明，DOI（5-HT 2A/2C受体激动剂）激活mPFC中5-HT 2A受体引起的局部5-HT释放增加可被5-HT 1A受体激动剂逆转。这种抑制作用被WAY-100635和大鼠中5-HT 1A受体的预先失活所拮抗，并且在缺乏5-HT 1A受体的小鼠中不存在。这些观察有助于澄清mPFC和中缝核之间的相互作用，这是精神疾病的两个关键领域，并提高我们对非典型抗精神病药物作用的理解，通过这些5-HT受体起作用。
The prefrontal cortex plays a key role in the control of higher brain functions and is involved in the pathophysiology and treatment of schizophrenia. Here we report that similar to60% of the neurons in rat and mouse prefrontal cortex express 5-HT1A and/or 5-HT2A receptor mRNAs, which are highly co-localized (similar to80%). The electrical stimulation of the dorsal and median raphe nuclei elicited 5-HT1A-mediated inhibitions and 5-HT2A-mediated excitations in identified pyramidal neurons recorded extracellularly in rat medial prefrontal cortex (mPFC). Opposite responses in the same pyramidal neuron could be evoked by stimulating the raphe nuclei at different coordinates, suggesting a precise connectivity between 5-HT neuronal subgroups and 5-HT1A and 5-HT2A receptors in pyramidal neurons. Microdialysis experiments showed that the increase in local 5-HT release evoked by the activation of 5-HT2A receptors in mPFC by DOI (5-HT2A/2C receptor agonist) was reversed by co-perfusion of 5-HT1A agonists. This inhibitory effect was antagonized by WAY-100635 and the prior inactivation of 5-HT1A receptors in rats and was absent in mice lacking 5-HT1A receptors. These observations help to clarify the interactions between the mPFC and the raphe nuclei, two key areas in psychiatric illnesses and improve our understanding of the action of atypical antipsychotics, acting through these 5-HT receptors.