There are four major dopamine pathways, each with distinct functions.
A. Mesolimbic Pathway
- From: Ventral tegmental area (VTA)
- To: Nucleus accumbens (limbic system)
- Function: Reward, pleasure, motivation
- Clinical Relevance: Overactivity is linked to positive symptoms of schizophrenia (e.g., hallucinations, delusions)
B. Mesocortical Pathway
- From: VTA
- To: Prefrontal cortex
- Function: Cognition, emotion, executive function
- Clinical Relevance: Underactivity is linked to negative symptoms of schizophrenia (e.g., flat affect, social withdrawal)
C. Nigrostriatal Pathway
- From: Substantia nigra (pars compacta)
- To: Dorsal striatum (caudate and putamen)
- Function: Initiation and control of movement
- Clinical Relevance: Dopamine blockade here causes extrapyramidal symptoms (EPS)
D. Tuberoinfundibular Pathway
- From: Hypothalamus
- To: Pituitary gland
- Function: Inhibits prolactin secretion
- Clinical Relevance: Dopamine blockade increases prolactin levels → galactorrhea, amenorrhea
Extrapyramidal Side Effects (EPS)
These are drug-induced movement disorders caused primarily by dopamine D2 receptor antagonism in the nigrostriatal pathway, usually due to antipsychotics (especially typical ones like haloperidol).
| Type | Description | Onset |
|---|---|---|
| Acute Dystonia | Muscle spasms, especially in face/neck | Hours to days |
| Akathisia | Inner restlessness, pacing | Days to weeks |
| Parkinsonism | Tremor, rigidity, bradykinesia | Weeks to months |
| Tardive Dyskinesia | Involuntary movements (lip smacking, grimacing) | Months to years (often irreversible) |
Mechanism:
Blockade of D2 receptors in the nigrostriatal pathway reduces dopaminergic control over movement, leading to imbalance between dopamine and acetylcholine causes EPS.
Treatment:
- Anticholinergics: e.g., benztropine, trihexyphenidyl (esp. for dystonia, parkinsonism)
- Beta-blockers: e.g., propranolol (for akathisia)
- Switch to atypical antipsychotics: e.g., clozapine, quetiapine (less EPS risk)
- VMAT2 inhibitors: e.g., valbenazine (for tardive dyskinesia)
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