Serotonin is also known as 5-hydroxytryptamine (5-HT). Serotonin was named because of its activity as a vasoconstrictor in the blood. Two percent of the body’s serotonin is located in the brain, where the highest concentration is in the raphe nuclei of the brainstem [7]. The neurons project widely throughout the CNS. Serotonin is a principal neurotransmitter that is involved in the regulation of many biological functions including anxiety, mood, sleep, appetite, memory, cognition, and sexual behavior [8].
Neurons in the brain synthesize serotonin. The amino acid tryptophan is hydroxylated by the enzyme tryptophan hydroxylase, forming 5-hydroxytryptophan. This is then decarboxylated to 5-hydroxytryptamine, or serotonin [7]. The precursor tryptophan comes primarily from diet, and it crosses the blood–brain barrier. The enzyme tryptophan hydroxylase is the rate-limiting step in serotonin synthesis. Termination of serotonin effects in the synaptic cleft occurs by way of the 5-HT transporter. 5-Hydroxytryptamine is taken up into the presynaptic terminals and goes back into storage vesicles or is metabolized.
Medications such as SSRIs and many tricyclic antidepressants (TCAs) bind to the transporter and block the reuptake of 5-HT. This leads to an increase in 5-HT levels in the synapse and starts a cascade of effects downstream. The SSRIs and serotonin (5-HT) bind to the same transporter site [6].