EATING DISORDER AND EPILEPSY IN MICE LACKING 5-HT2C SEROTONIN RECEPTORS
EATING DISORDER AND EPILEPSY IN MICE LACKING 5-HT2C SEROTONIN RECEPTORS
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DOI：
10.1038/374542a0
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发表时间：
1995-04-06
期刊：
影响因子：
64.8
通讯作者：
JULIUS, D
中科院分区：
文献类型：
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作者：
TECOTT, LH;SUN, LM;JULIUS, D
血清素（5-羟色胺，5-HT）是一种单胺能神经递质，据信可调节哺乳动物神经系统中的许多感觉、运动和行为过程（1-3）。这些不同的反应是通过激活一个大家族的受体亚型引起的（4）。这种信号系统的复杂性和选择性药物的缺乏使得很难定义5-HT受体亚型的特定作用，或确定哪些多巴胺能药物调节情绪和行为。为了解决这些问题，我们已经产生了缺乏功能性5-HT 2C受体（以前称为5-HT 1C）的突变小鼠，该受体是在整个大脑和脊髓中广泛表达的突出的G蛋白偶联受体，并且已经提出介导血清素的许多中枢神经系统（CNS）作用（3.5-6）。在这里，我们表明，5-HT 2C受体缺陷的小鼠超重的结果异常控制的喂养行为，建立一个角色，这种受体在食欲的神经递质控制。突变的动物也容易自发死亡的癫痫发作，这表明5-HT 2C受体介导的紧张性抑制神经网络的兴奋性。
SEROTONIN (5-hydroxytryptamine, 5-HT) is a monoaminergic neurotransmitter that is believed to modulate numerous sensory, motor and behavioural processes in the mammalian nervous system(1-3). These diverse responses are elicited through the activation of a large family of receptor subtypes(4). The complexity of this signalling system and the paucity of selective drugs have made it difficult to define specific roles for 5-HT receptor subtypes, or to determine bow serotonergic drugs modulate mood and behaviour. To address these issues, we have generated mutant mice lacking functional 5-HT2C receptors (previously termed 5-HT1C), prominent G-protein-coupled receptors that are widely expressed throughout the brain and spinal cord and which have been proposed to mediate numerous central nervous system (CNS) actions of serotonin(3.5-6). Here we show that 5-HT2C receptor-deficient mice are overweight as a result of abnormal control of feeding behaviour, establishing a role for this receptor in the serotonergic control of appetite. Mutant animals are also prone to spontaneous death from seizures, suggesting that 5-HT2C receptors mediate tonic inhibition of neuronal network excitability.