The serotonin–dopamine interaction is critical for fast-onset action of antidepressant treatment: in vivo studies in an animal model of depression

Abstract

In the last decade, many new antidepressants have been developed that display a more rapid onset to clinical effects than classical antidepressants. However, the mechanism that enables some drugs to have a faster onset of action than others is poorly understood. The aim of the present study was to determine neural alterations that are specific to fast-acting antidepressant action using Flinders Sensitive Line (FSL) rats, an animal model of depression. Because of the central role of accumbal dopamine in the mediation of motivation and reward, our measurements were focused on dopaminergic neurotransmission in the nucleus accumbens (NAC). The authors found that 7-day treatment with nefazodone (a putative fast-onset antidepressant) but not with desipramine (a classical antidepressant) normalized immobility time in the swim test in FSL rats. Serotonin (5-HT)-induced dopamine release but not basal dopamine levels correlated with the improvement of depressive-like behavior. The authors conclude that the 5-HT–dopamine interaction is critical to the fast-onset action of antidepressant treatment.