Association between depressive behavior and absence of serotonin-dopamine interaction in the nucleus accumbens

Rationale: Current hypotheses on the etiology of depression attribute the d isorder to alterations in serotonin and norepinephrine neurotransmission. H owever, the relationship between these alterations and depressive behavior is poorly understood. Conversely, an interaction between the serotonergic a nd dopaminergic systems in the nucleus accumbens has been established. Sinc e motivation and hedonia have been associated with dopamine release in the nucleus accumbens, we decided to test its modulation by serotonin in relati on to depressive-like behavior. Objectives and methods: The extracellular d opamine levels in the nucleus accumbens were studied in vivo in Flinders Se nsitive Line (FSL, a rat model of depressive behavior) and control rats, be fore and after antidepressant treatment. Rats were chronically treated with the antidepressants desipramine (5 mg/kg/day) and paroxetine:(7.5 mg/kg/da y) for 18 consecutive days. As a measure of depressive behavior we used a m odified swim test. The release of dopamine in response to local serotonin a pplication was monitored using the microdialysis technique. Results: Seroto nin (0.5 muM) facilitated dopamine release in the nucleus accumbens of cont rol rats. In FSL rats, basal extracellular dopamine levels in the nucleus a ccumbens were 40% lower than in control rats and did not increase in respon se to serotonin stimulation. However, chronic antidepressant treatment of t he FSL rats normalized the serotonin-dopamine interaction as well as their behavioral deficiencies. Conclusions: The inability of serotonin to stimula te dopamine release in the nucleus accumbens, thereby leading to anhedonia and lack of motivation, may therefore be an essential factor in the onset o f depression and a target for modulation by: antidepressant drugs.