The 5-HT2C receptor as a target for mood disorders

The serotonin (5-hydroxytryptamine2C [5-HT2C]) receptor is one of the 5-HT receptors with a G-protein-coupled intracellular signalling pathway. A large number of compounds showing antidepressive, antipsychotic and anxiolytic properties, and affecting sleep patterns, feeding behaviour and neuroendocrine functions, target this subtype of receptor. The potential use of 5-HT2C receptor ligands in psychiatry has been suggested as a result of a number of observations from animal and in vitro experiments. The results of studies performed suggest that some of the therapeutic effects of the selective serotonin re-uptake inhibitors (SSRIs) may be mediated, at least in part, by the 5-HT2C receptor. The long-term downregulation of 5-HT2C receptors is associated with their interaction with some SSRIs and may lead to disinhibition of the mesolimbic dopamine system, which may be partly responsible for their antidepressant action. Nevertheless, current evidence does not allow complete definition of 5-HT2C receptor functions and properties. Concerning genetics, there are no unequivocal results for the involvement of polymorphisms of the 5-HT2C receptor, and no studies on their association with an antidepressant response have ever been performed. This paper reviews some of the studies on this 5-HT receptor subtype, focusing on its possible importance as a target for mood disorder therapy.