MECHANISMS AND REGULATION OF 5HT RECEPTORS IN THE CNS

5-羟色胺是哺乳动物体内普遍存在的神经递质 个脑袋 因此，它已被牵连在许多控制 行为和精神疾病的病理生理学， 抑郁症和强迫症。 人们早就 认识到血清素通过多种受体起作用， 在大脑中发挥作用。 因此特定 5-羟色胺受体亚型一直被认为是有前途的 治疗干预的目标。 努力执行这些 然而，由于我们的理解有限， 由不同的血清素受体亚型介导的作用 在大脑里。 本提案旨在通过以下方式解决这一问题： 阐明两种5-羟色胺受体的作用机制 亚型介导兴奋性反应的血清素在 个脑袋 5-羟色胺在体外大鼠脑片中的作用将在 研究使用全细胞记录电生理 技术. 具体来说，我们将研究 5-羟色胺对前丘脑的去甲肾上腺素神经元， 前额皮质 我们假设这些表面上 类似的反应涉及5-HT 7的两种不同受体 和5-H2 A亚型。 此外，我们假设， 这些反应也将通过不同的细胞介导， 和离子机制。 这些研究应该阐明特定的 5-羟色胺受体亚型调节细胞膜兴奋性 中枢神经系统 因此，他们应该为我们的 了解血清素在大脑中的作用。 这 知识应该有助于指导发展 靶向多巴胺能系统的新治疗策略 大脑

Serotonin is a ubiquitous neurotransmitter in the mammalian brain. As such it has been implicated in the control of many behaviors and in the pathophysiology of mental diseases such as depression and obsessive compulsive disorders. It has long been recognized that serotonin acts through a variety of receptor subtypes to exert its effects in the brain. Thus specific serotonin receptor subtypes have long been regarded as promising targets for therapeutic intervention. Efforts to implement such interventions, however, are hampered by our limited understanding of the actions mediated by different serotonin receptor subtypes in the brain. This proposal seeks to address this issue by elucidating the mechanism of actions of two serotonin receptor subtypes that mediate excitatory responses to serotonin in the brain. The effects of serotonin in in vitro rat brain slices will be investigated using whole cell recording electrophysiological techniques. Specifically we will investigate the ability of serotonin to depolarize neurons of the anterior thalamus and prefrontal cortex. We hypothesize that these superficially similar responses involve two different receptors of the 5-HT7 and 5-H2A subtypes respectively. Furthermore we hypothesize that these responses will also be mediated though different cellular and ionic mechanisms. These studies should elucidate the mechanisms by which specific serotonin receptor subtypes regulate membrane excitability in the central nervous system. As such they should contribute to our understanding of the actions of serotonin in the brain. This knowledge should prove helpful in guiding the development of novel therapeutic strategies targeting serotonergic systems in the brain.