The 5-HT3 receptor subtype is a ligand-gated ion channel that controls dopamine release. It is a common target of antiemetic therapy, as well as other psychoactive drugs. A high density of 5-HT3 receptors has been identified in the human brainstem, particularly in the area postrema (the putative vomiting center of the brain) and the nucleus tractus solitarius. Lower levels of expression of the 5-HT3 receptor have been shown in the limbic system, hippocampus and the cerebral cortex.
The 5-HT4 receptor subtype is coupled to a G-protein that stimulates the intracellular messenger adenylate cyclase that, in turn, regulates neurotransmission. In the human brain, a high density of 5-HT4 receptors has been identified in the striato-nigral system, notably in the caudate nucleus, lenticular nucleus (putamen and globus pallidus) and the substantia nigra. Lower levels of expression of the 5-HT4 receptor have been shown in the hippocampus and the frontal cortex.
The 5-HT6 and 5-HT7 subtypes of serotonin receptor are coupled to a G-protein that stimulates the intracellular messenger adenylate cyclase that, in turn, regulates neurotransmission. In the human brain, a high density of -5HT6 receptors has been identified in the olfactory tubercle, corpus striatum, nucleus accumbens, dentate gyrus and hippocampus. Lower levels of expression of the 5-HT6 receptor have been shown in the cerebellum and amygdala. Studies in the rat suggest the 5-HT7 receptor is widely distributed in the brain; examination of human brain tissue has shown expression in the thalamus.
There are seven sub-types of 5-HT receptor and the 1A subtype is widely expressed throughout the brain. The highest levels of this sub-type are found in the hippocampus and medial temporal cortex, with slightly lower levels in the pre-frontal cortex. Low levels of 5-HT1A are found in the basal ganglia.
In depression the density of 5-HT1A receptors is altered compared with the normal brain. The 5-HT1A receptor density is increased in the hippocampus and medial temporal cortex, while the density of these receptors is reduced compared with normal in the cerebellum, basal ganglia and prefrontal cortex.
There are seven main types of serotonin receptors in the brain. The 5-HT2 receptors (A, B and C subtypes) are widely distributed throughout the brain. Briefly, these receptors can be found in the cerebral cortex, amygdala, hypothalamus, hippocampus, substantia nigra, choroid plexus, substantia innominata and some components of the basal ganglia.
In depression the distribution of 5-HT2 receptors is altered compared with the normal brain. The 5-HT2 receptor density is decreased in the frontal, temporal, parietal and occipital cortical regions compared with normal. 5-HT2 expression in the hippocampus, basal ganglia, substantia nigra, hypothalamus, choroid plexus and substantia innominata remains unaffected by depression.
In depression the distribution of 5-HT2 receptors is altered compared with the normal brain. The 5-HT2 receptor density is decreased in the frontal, temporal, parietal and occipital cortical regions compared with normal. 5-HT2 expression in the hippocampus, basal ganglia, substantia nigra, hypothalamus, choroid plexus and substantia innominata remains unaffected by depression.