Dopamine and the diseased brain

Abstract

Dysfunction of central dopaminergic neurotransmission has been implicated in a series of neuropsychiatric disorders, including Tourette's syndrome, schizophrenia, and drug and alcohol dependence. The behavioral and psychopathological manifestations of central dopaminergic dysfunction differ depending on the site of their neurobiological correlate. These sites may be found in the dorsal or ventral striatum, but also in cortical regions such as the limbic and prefrontal cortex, among other locations. A low basic dopamine turnover and an increase in the availability of dopamine D2 receptors in the caudate body have been associated with the severity of motor tics in Tourette's syndrome. In the ventral striatum and particularly in the nucleus accumbens, different drugs of abuse stimulate dopamine release and thus reinforce drug consumption. The downregulation of dopamine D2 receptors in this area of the brain has been associated with alcohol craving and an increase in the processing of alcohol-related stimuli in the medial prefrontal cortex. Brain imaging studies in which intrasynaptic dopamine release is manipulated in vivo have shown that increased subcortical dopamine release is associated with the pathogenesis of positive symptoms in schizophrenia. This review discusses a broad range of brain imaging and neuroendocrinological studies on dopaminergic dysfunction in neuropsychiatric disorders, including relevant findings on the basis of primate studies. In addition, the hypothesis is examined that phasic dopamine release is associated with salience attribution to external stimuli, insofar as it mediates reward anticipation in the ventral striatum and limbic cortex, habit formation in the dorsal striatum, and working memory function in the prefrontal cortex.