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

LH Tecott, LM Sun, SF Akana, AM Strack… - Nature, 1995 - nature.com
LH Tecott, LM Sun, SF Akana, AM Strack, DH Lowenstein, MF Dallman, D Julius
Nature, 1995nature.com
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 system1-3. 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 …
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 system1-3. 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-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 serotonin3,5-8. Here we show that 5-HT2Creceptor-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 inhi-bition of neuronal network excitability.
nature.com