The role of dopamine in the biological basis of dysthymia

This paper reviews the recent literature supporting the hypothesis that a reduced neurotransmission in the mesolimbic dopamine (DA) system may sustain some of the core and subsidiary symptoms of dysthymia and other depressive conditions, namely anhedonia, lack of interest, lack of drive, lack of concentration, and psychomotor retardation. Experimental evidence indicates that mesolimbic DA mediates the rewarding; motivating and incentive effect of natural and artificial stimuli such as sex, foods, liquids, intracranial self-stimulation, and the drugs such as cocaine and amphetamine. Conversely, it has been shown that withdrawal from chronic treatment with these drugs is associated with depressive symptomatology and reduced release of DA in the ventral striatum. Similarly, different models of depression such as 'behavioral despair', 'learned helplessness' and 'chronic mild stress' are associated with reduced DA activity in the limbic system, which is reversed by chronic treatment with antidepressants. Various antidepressants, irrespective of their acute action on the uptake of specific neurotransmitters such as noradrenaline, serotonin and DA, when given chronically have the common property of potentiating the behavioral responses to psychostimulants that are mediated by DA receptors in the limbic areas. The DA hypothesis of depression offers a logical explanation for the antidepressive effect of drugs such as sulpiride and amisulpride, which block DA autoreceptors and thus increase DA output.