Figure 2. The Dopamine Hypothesis of Schizophrenia.
(A) Organization of the nigrostriatal and mesocortical midbrain dopaminergic projections. The dopaminergic midbrain neurons topographically project to the striatum but with an inverse dorsal-to-ventral organization. The mesocortical projections arise from the dorsal and medial dopamine cells.
(B) The original dopamine hypothesis of schizophrenia. The original dopamine hypothesis proposed that a global hyperactivity of the dopaminergic projections in the brain may lead to the symptoms of schizophrenia.
(C) The revised dopamine hypothesis of schizophrenia. The revised dopamine hypothesis proposed that a hyperactive nigrostriatal dopaminergic projection leads to positive symptoms but a hypoactive mesocortical projection is responsible for cognitive and negative symptoms.
(D) Results of brain imaging studies in schizophrenia. Brain imaging studies show that an increase in amphetamine-induced dopamine release in the striatum is highest in the associative striatum. Moreover, the density and occupancy of striatal D2 receptors is increased in drug-free or drug-naive patients.
PFC, prefrontal cortex; dSTR, dorsal striatum; vSTR, ventral striatum; VTA, ventral tegmental area; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; D2R, dopamine D2 receptor.