in a certain population of patients. Activation of 5-HT2C by serotonin is responsible for many of the negative side effects of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine, and others. Some of the initial anxiety caused by SSRIs is due to excessive signalling at 5-HT2C. Over a period of 1–2 weeks, the receptor begins to downregulate, along with the downregulation of 5-HT2A, 5-HT1A, and other serotonin receptors. This downregulation parallels the onset of the clinical benefits of SSRIs. 5-HT2C receptors exhibit constitutive activity in vivo, and may retain the ability to influence neurotransmission in the absence of ligand occupancy. Thus, 5-HT2C receptors do not require binding by a ligand (serotonin) in order to exhibit influence on neurotransmission. Inverse agonists may be required to fully extinguish 5-HT2C constitutive activity, and may prove useful in the treatment of 5-HT2C-mediated conditions in the absence of typical serotonin activity. In addition to the evidence for a role of 5-HT2C receptor stimulation in depressive symptoms there also is evidence that activation of 5-HT2C receptors may have beneficial effects upon certain aspects of depression, one group of researchers found that direct stimulation of 5-HT2C receptors with a 5-HT2C agonist reduced cognitive deficits in mice with a TPH2 loss-of-function mutation. 5-HT2C receptors mediate the release and increase of extracellular dopamine in response to many drugs, including caffeine, nicotine, amphetamine, morphine, cocaine, and others. 5-HT2C antagonism increases dopamine release in response to reinforcing drugs, and many dopaminergic stimuli. Feeding, social interaction, and sexual activity all release dopamine subject to inhibition of 5-HT2C. Increased 5-HT2C expression reduces dopamine release in both the presence and absence of stimuli. Conditions that increase cytokine levels in the human body may have potential to raise 5-HT2C gene expression in the brain. This could possibly comprise a link between viral infections and associated depression. Cytokine therapy has been shown to increase 5-HT2C gene expression, resulting in increased activity of 5-HT2C receptors in the brain . Endocrinology Serotonin is involved in basal and stress-induced regulation of hypothalamus and pituitary gland hormones such as prolactin, adrenocorticotropic hormone (ACTH), vasopressin and oxytocin, mainly via actions of receptor subtypes 5-HT2A and 5-HT2C. Therefore, the 5-HT2C receptor is a significant modulator of the hypothalamic–pituitary–adrenal axis (HPA axis). The HPA axis is the main controller of acute sympathetic stress responses related to fight-or-flight response. Prolonged activation and disturbances of the HPA axis contribute to depressive and anxiety symptoms