Serotonin is an important neurotransmitter responsible for several brain functions. It is chemically categorized, along with dopamine and norepinephrine, as a monoamine neurotransmitter, which means a single amine functional group is in its structure. Serotonin is metabolized from trypamine, an amino acid and, based on its chemical structure, is also called 5-hydroxytryptamine, or 5-HT. The various functions of serotonin are mediated through its activation of proteins in the brain called receptors. Fifteen serotonin receptor subtypes have been identified, and they are categorized along the lines of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT7. Much more is known about some serotonin receptors than others.
History
According to a report by the American College of Neuropsychopharmacology on serotonin receptor subtypes and ligands (drugs that bind to these receptors), serotonin was discovered in the 1940s. Soon after, scientists realized that serotonin was biologically active. In the 1960s and 1970s, research revealed initial receptors for serotonin, the 5-HT1 and 5-HT2 receptors. With the molecular biology revolution of the 1980s, several more serotonin receptors were cloned, and now 15 subtypes of serotonin receptors have been identified.
Types: 5-HT1A Receptors
According to Dr. Richard Glennon and colleagues, 5-HT1A receptors are important in a number of different functions, including memory, fear, anxiety, depression and cognition. Accordingly, medications that target the 5-HT1A receptor are largely used to modulate pathological manifestations of these functions. For example, the drug Buspar (buspirone) is prescribed for the treatment of anxiety and depression.
Types: 5-HT2A Receptors
Glennon and colleagues have also reviewed the properties of 5-HT2A receptors. Probably deriving from the functions of the brain regions in which these receptors are expressed, drugs that activate 5-HT2A receptors are often hallucinogens. Lysergic acid diethylamide (LSD), mescaline (the active ingredient in the peyote cactus) and psilocybin (the active ingredient in hallucinogenic mushrooms) all activate 5-HT2A receptors. Several other hallucinogenic drugs exist, and their affinity for binding to the 5-HT2A receptor predicts their potency to produce hallucinogenic effects in humans.
Types: 5-HT2C Receptors
The 5-HT2C receptor has been implicated in many functions, including migraines, eating disorders, epilepsy, anxiety and drug relapse. Furthermore, the specific functions of this receptor have been particularly difficult to establish because of the lack of available drugs that target this receptor. Many drugs that target both the 5-HT2C and 5-HT2A (and the 5-HT2B) receptor such as ketanserin, ritanserin and mianserin have been available for a couple of decades, but drugs that selectively target this receptor have only recently become available. With the development of selective experimental compounds, such as SB-242084, further research will allow scientists to more fully characterize the functions of this receptor.
Types: Other Serotonin Receptors
Several serotonin receptors are less understood than the examples already mentioned. For example, 5-HT3 receptors are involved in emesis (vomiting), and drugs that antagonize this receptor, such as ondansetron, have anti-emetic effects. However, this receptor might have important roles in other processes, such as reducing the effects of stimulant-type drugs of abuse. As another example, scientists discovered and cloned the 5-HT4-7 receptors more recently than other serotonin receptors, and we know even less about them. Further research and drug development efforts are under way to more fully illuminate the brain distributions and functions of these receptors, as well as the clinical potential for drugs that target them.
Where are Serotonin Receptors in the Brain
Serotonin receptors are expressed in a large variety of brain regions. The regions in which they are expressed have important implications for their function. According to a review article published in the journal Neuropharmacology, 5-HT1A are expressed in the hippocampus, amygdala and cortex. 5-HT2A receptors are expressed in many parts of the brain, but are expressed in the highest densities in the neocortex. The 5-HT2C receptor is also expressed in a large number of brain areas, but it is particularly abundant in the hypothalamus and the midbrain.
Expert Insight
Serotonin is a fascinating neurotransmitter. Other neurotransmitters could be argued to mediate more mundane functions. For example, the neurotransmitter norepinephrine is important for cardiovascular functions such as heart rate. In contrast, serotonin mediate functions as interesting as mood, perception, and cognition. These functions are central to our sense of self and to human consciousness.
