Effects of chronic antidepressant treatment on pre- and post-synaptic dopaminergic mechanisms. A short review of the literature and some complementary experiments.

The evidence for alterations in the dopaminergic system in animals induced by repetitive antidepressant treatment is discussed. Drugs with dopamine (DA) antagonistic, uptake inhibiting or releasing properties can be expected to cause receptor super- or subsensitivity, resp. MAO inhibitors cause a sustained suppression of DA synthesis due to direct inhibition of tyrosine hydroxylase by elevated cytosolic DA. With desipramine iprindol, electroconvulsive shock and REM sleep deprivation, there is some evidence for a development of postsynaptic DA receptor supersensitivity; this might, however, be secondary to effects of these treatments on the noradrenergic system. Nevertheless, it could play a role in the therapeutic effects of antidepressant treatments, in view of the role which the mesolimbic DA system seems to play in reinforcement and reward processes. Subsensitivity of presynaptic DA receptors was reported by two research groups to be caused by a variety of antidepressant treatments on the basis of biochemical, behavioural and electrophysiological data. Others were unable to reproduce or corroborate these findings. Taking into account the information hitherto available, the evidence for the development of presynaptic DA receptor subsensitivity after antidepressant treatment is not considered convincing.