EATING DISORDER AND EPILEPSY IN MICE LACKING 5-HT2C SEROTONIN RECEPTORS

SEROTONIN (5-hydroxytryptamine, 5-HT) is a monoaminergic neurotransmit ter that is believed to modulate numerous sensory, motor and behaviour al processes in the mammalian nervous system(1-3). These diverse respo nses 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 fo r 5-HT receptor subtypes, or to determine bow serotonergic drugs modul ate mood and behaviour. To address these issues, we have generated mut ant mice lacking functional 5-HT2C receptors (previously termed 5-HT1C ), prominent G-protein-coupled receptors that are widely expressed thr oughout the brain and spinal cord and which have been proposed to medi ate 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 f or this receptor in the serotonergic control of appetite. Mutant anima ls are also prone to spontaneous death from seizures, suggesting that 5-HT2C receptors mediate tonic inhibition of neuronal network excitabi lity.