Eating disorder and epilepsy in mice lacking 5-HT sub 2C serotonin receptors.
Tecott, Laurence H.; Sun, Linda M.; Akana, Susan F.; Strack, Alison M.; Lowenstein, Daniel H.; Dallman, Mary F.; Julius, David
[Letter]
Nature.
374(6522):542-546, April 6, 1995.
(Format: HTML)
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 how 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 [3,5-8]. Here we show that 5-HT sub 2C 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.
(C) 1995 Macmillan Magazines Ltd.