1. Dopamine system: neuroanatomy
Dopamine neurons have 4 major projections:
1. Nigrostriatal pathway
Substantia nigra (SNc; A9)  caudate and putamen (i.e. striatum). Motor (involuntary) control
Parkinson's Disease
2. Mesolimbic pathway
Ventral Tegmental Area (VTA; A10) in midbrain to limbic regions associated with reward, motivation, affect and memory
Include ventral striatum (nucleus accumbens), amygdala, hippocampus & medial prefrontal cortex
3. Mesocortical pathway
VTA to frontal cortex, including dorsolateral prefrontal cortex (DLPFC)
cognitive function, motivation & emotional response
4. Tuberoinfundibular pathway
Tuberal region to median eminence (infundibular region at top of pituitary stalk)
DA acts to inhibit prolactin release from pituitary 3 1 2 4 1 1

2. DA abnormalities in schizophrenia
Excessive DA release in striatum during illness exacerbations
Positively correlated with positive symptoms (1)
Correlated with good treatment response to antipsychotic drugs (2)
Inadequate DA in frontal cortex
Associated with deficits in cognitive function e.g. working memory (3) 3 2 1 4
DA dysregulation not thought to be a primary abnormality. Secondary to a more proximal abnormality e.g. in GABA or glutamate systems.
1. Laruelle & Abi-Dargham, J Psychopharmacol 13;
2. Abi-Dargham et al, PNAS 97:
3. Abi-Dargham et al, J Neurosci 22: 2 2