5-HT2A/2C receptor blockade regulates progenitor cell proliferation in the adult rat hippocampus
5-HT2A/2C receptor blockade regulates progenitor cell proliferation in the adult rat hippocampus
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DOI：
10.1016/j.neulet.2008.06.028
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发表时间：
2008-08-22
影响因子：
2.5
通讯作者：
Vaidya, Vidita A.
中科院分区：
文献类型：
--
作者：
Jha, Shanker;Rajendran, Rajeev;Vaidya, Vidita A.
据报道，成年海马区神经发生是抗抑郁药物、滥用药物和抑郁症动物模型的靶点，这表明这种形式的结构可塑性在精神病理学中具有作用。5-羟色胺能神经传递与多种精神疾病有关，据报道，5-羟色胺能神经传递调节成年海马神经发生。在5-羟色胺能受体中，5-羟色胺(2A/2C)(5-羟色胺(2A/2C)受体在抗抑郁药物的作用和致幻药物滥用的作用中起着重要的作用。我们使用有丝分裂标志物5‘-溴-2-脱氧尿苷来研究5-羟色胺(2A/2C)受体在致幻部分激动剂(+/-)-2，5-二甲氧基-4-碘苯丙胺(DOI)和麦角酸二乙胺(LSD)及其拮抗剂酮丝林急性或慢性处理后对成年海马祖细胞增殖的影响。急性和慢性DOI和LSD治疗诱导了强烈的行为激活，但不改变成年海马祖细胞的增殖。与之形成鲜明对比的是，Ketanserin治疗导致一次治疗后祖细胞增殖显著下降(22%)，而在长期给药后显著增加(46%)。这些结果表明，与其他滥用药物相比，主要针对5-羟色胺(2A/2C)受体的致幻药物可能不会改变成人海马神经发生。此外，我们的结果表明，5-羟色胺(2A/2C)受体的持续阻断导致成年海马祖细胞的增殖增强，这表明5-羟色胺(2A/2C)受体可能是抗抑郁药物治疗的一个重要的神经源性作用靶点。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Adult hippocampal neurogenesis is reported to be a target of antidepressants, drugs of abuse and animal models of depression, suggesting a role for this form of structural plasticity in psychopathology. Serotonergic neurotransmission, which is implicated in several psychiatric diseases, has been reported to regulate adult hippocampal neurogenesis. Amongst the serotonergic receptors, the serotonin(2A/2C) (5-HT(2A/2C) receptors play an important role in the actions of antidepressants and the effects of hallucinogenic drugs of abuse. We have used the mitotic marker 5'-bromo-2-deoxyuridine to address the effects of the 5-HT(2A/2C) receptors on the proliferation of adult hippocampal progenitors following acute or chronic treatment with the hallucinogenic partial agonists, (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) and lysergic acid diethylamide (LSD) and the antagonist, Ketanserin. Acute, and chronic, DOI and LSD treatments induced a strong behavioral activation, but did not alter adult hippocampal progenitor proliferation. In striking contrast, Ketanserin treatment resulted in a biphasic regulation with a significant decline (22%) in progenitor proliferation following a single treatment, and a robust increase (46%) observed following chronic administration. These results indicate that hallucinogenic drugs that primarily target the 5-HT(2A/2C) receptors, in contrast to other drugs of abuse, may not alter adult hippocampal neurogenesis. In addition, our results that enhanced adult hippocampal progenitor proliferation results from a sustained blockade of the 5-HT(2A/2C) receptors suggest that the 5-HT(2A/2C) receptors may be an important target for the neurogenic effects of antidepressant treatment. (C) 2008 Elsevier Ireland Ltd. All rights reserved.