dopamine

Dopamine is a monoamine neurotransmitter in the brain and a peripheral modulator in the autonomic nervous system. It is a catecholamine named 4,5-dihydroxyphenethylamine and is synthesized from the amino acid tyrosine through a two-step process: tyrosine is converted to L-DOPA by tyrosine hydroxylase, and L-DOPA is decarboxylated to dopamine.

In the brain, dopaminergic neurons are concentrated in the substantia nigra and the ventral tegmental area. Dopamine signals through five receptors, grouped into D1-like (D1, D5) and D2-like (D2, D3, D4) families. D1-like receptors activate adenylate cyclase, while D2-like receptors inhibit it. Dopaminergic signaling includes phasic bursts and tonic activity, and dopamine action is terminated primarily by reuptake via the dopamine transporter (DAT) and by enzymatic breakdown through monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).

Major dopaminergic pathways include the nigrostriatal tract, which supports movement and habit formation; the mesolimbic and mesocortical pathways, which underlie reward, motivation, learning, and executive function; and the tuberoinfundibular pathway, which regulates prolactin secretion.

Dopamine influences motor control, reward processing, motivation, attention, and mood, and it modulates endocrine function via prolactin inhibition. Dysregulation is associated with several disorders: degeneration of nigrostriatal dopamine in Parkinson disease; hyperdopaminergic signaling in mesolimbic pathways contributing to symptoms of schizophrenia; reduced dopaminergic activity linked to anhedonia in depression; and involvement in attention-deficit/hyperactivity disorder and substance use disorders.

Pharmacologically, L-DOPA remains a primary treatment for Parkinson disease; dopamine receptor agonists and antagonists are used clinically; drugs that affect dopamine reuptake (DAT inhibitors) or metabolism (MAO/COMT inhibitors) modify its signaling.