serotonergic

Serotonergic refers to anything related to serotonin, a monoamine neurotransmitter known as 5-hydroxytryptamine (5-HT). In the brain, serotonergic neurons mainly arise from the raphe nuclei in the brainstem and project widely to cortical and subcortical regions; in the periphery, serotonin is abundant in enterochromaffin cells of the gut and in platelets.

Serotonin is synthesized from tryptophan by the enzymes tryptophan hydroxylase and aromatic L-amino acid decarboxylase, and it is inactivated primarily by reuptake via the serotonin transporter (SERT) and degraded by monoamine oxidase A to 5-hydroxyindoleacetic acid (5-HIAA). Serotonin signals through a family of receptors designated 5-HT1 through 5-HT7, with multiple subtypes. Most receptors are G protein–coupled, whereas 5-HT3 is a ligand-gated ion channel. Activation of these receptors influences mood, anxiety, sleep, appetite, pain modulation, thermoregulation, and cognition.

Functionally, central serotonergic signaling modulates mood, arousal, appetite, learning, and pain processing, while peripheral serotonin regulates gut motility, vascular tone, and platelet aggregation. Abnormal serotonergic signaling has been linked to several disorders, including depression, anxiety disorders, obsessive-compulsive disorder, PTSD, and migraine.

Pharmacologically, the serotonergic system is targeted by drugs such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) that increase synaptic 5-HT, and triptans that selectively activate 5-HT1B/1D receptors for migraine relief. Psychedelic compounds act on 5-HT receptors, notably 5-HT2A. Serotonin syndrome is a potential risk with excessive serotonergic activity or drug interactions. The term serotonergic describes neurons, receptors, pathways, or pharmacologic effects related to serotonin transmission.