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).

• Cognition and executive functions (DLPFC), emotions and affect (VMPFC).

• 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.

• 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.

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