Dopamine pathways & antipsychotics

Flavio Guzmán, MD
Pharmacology Instructor
Health Sciences Faculty
University of Mendoza
Argentina

Psychiatry Resident
Mental Health Teaching Hospital “Dr. Carlos Pereyra “
Mendoza
Argentina
 Learning objective
• Understand basic concepts of dopaminergic
pathways and their relevance to
antipsychotic effects.
 Dopaminergic pathways: outline
- Mesolimbic pathway (positive
symptoms)
- Mesocortical pathway (negative
symptoms)
- Nigrostriatal pathway (EPS and
TD)
-Tuberoinfundibular pathway
(hyperprolactinemia)
Mesolimbic pathway & positive symptoms of schizophrenia
Anatomy

• Projections from the ventral

tegmental area (VTA) to the nucleus
accumbens.

Physiology

• Motivation, emotions, reward ,

positive symptoms of schizophrenia

Implications

• D2 antagonists reduce positive

symptoms of schizophrenia.
Mesocortical pathway: negative & cognitive symptoms

Anatomy

• Projections from the ventral tegmental

area (VTA) to the cortex (PFC).

Physiology

• Cognition and executive functions

(DLPFC), emotions and affect (VMPFC).

Implications

• Hypofunction of the mesocortical

pathway might be related to cognitive
and negative symptoms in schizophrenia
 Nigrostriatal pathway & EPS
Anatomy

• Projections from substantia nigra (pars

compacta) to striatum (caudate and
putamen).

Physiology

• Stimulation of purposeful movement.

Implications

• D2 antagonism induces
extrapyramidal symptoms
(pseudoparkinsonism)
Tuberoinfundibular pathway & prolactin release
Anatomy

• Hypothalamus (arcuate and periventricular

nuclei) to infundibular region (median
eminence).

Physiology

• Dopamine is released into the portal

circulation connecting the median eminence
with the anterior pituitary gland.
• Dopamine tonically inhibits prolactin
release.

Implications

• D2 antagonism increases prolactin levels.

 Summary
• Hyperactivation from the VTA to limbic areas might be
related to positive symptoms of schizophrenia.
• Hypofunction of the mesocortical pathway might in part
explain cognitive and negative symptoms of schizophrenia.
• D2 blockade of the nigrostriatal pathway can cause EPS.
• D2 blockade of the tuberoinfundibular pathway increases
prolactin blood levels.