Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors

Abstract

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 subtypes⁴. 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 behav-iour. To address these issues, we have generated mutant mice lacking functional 5-HT_2C receptors (previously termed 5-HT_1C), 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_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-HT_2C receptors mediate tonic inhi-bition of neuronal network excitability.