5-HT6 receptor

The 5-HT₆ receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). It is a G protein-coupled receptor (GPCR) that is coupled to G_s and mediates excitatory neurotransmission.HTR6 denotes the human gene encoding for the receptor.

Distribution

The 5-HT₆ receptor is expressed almost exclusively in the brain. It is distributed in various areas including, but not limited to, the olfactory tubercle, cerebral cortex (frontal and entorhinal regions), nucleus accumbens, striatum, caudate nucleus, hippocampus, and the molecular layer of the cerebellum. Based on its abundance in extrapyramidal, limbic, and cortical regions it can be suggested that the 5-HT₆ receptor plays a role in functions like motor control, emotionality, cognition, and memory.

Function

Blockade of central 5-HT₆ receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas, whereas activation enhances GABAergic signaling in a widespread manner. Antagonism of 5-HT₆ receptors also facilitates dopamine and norepinephrine release in the frontal cortex, while stimulation has the opposite effect.