Dopamine Signaling
Dopaminergic neurotransmission regulating reward, motivation, and motor control.
Overview
Dopamine is synthesized from tyrosine by tyrosine hydroxylase (TH) and DOPA decarboxylase, stored in vesicles by VMAT2, and released into the synaptic cleft. It acts on D1-like (D1, D5 — Gαs-coupled, stimulatory) and D2-like (D2, D3, D4 — Gαi-coupled, inhibitory) receptors. Dopamine is cleared by DAT (dopamine transporter) reuptake and metabolized by MAO and COMT. The mesolimbic pathway mediates reward, mesocortical controls cognition, and nigrostriatal controls movement.
Cellular Location
Midbrain dopaminergic neurons → target regions
Clinical Significance
Parkinson's disease = nigrostriatal dopamine loss (treated with L-DOPA); schizophrenia involves mesolimbic excess (D2 antagonists); addiction hijacks reward circuitry; ADHD involves prefrontal dopamine.