Abstract

The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic–hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic–pituitary–adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.

Highlights

  • Accumulating evidence suggests that hypofunction of the mesolimbic dopamine (DA) pathway is involved in major depression, in anhedonia and loss of motivation [1,2]

  • The aim of this study was to evaluate the changes in DAergic activity following two and four weeks of antidepressant treatment (ADT) using the COR response to APO as a probe of DAergic receptor responsiveness

  • All enrolled patients were treated with antidepressants at the time of hospital admission, and all were free of psychotropic drugs for at least 2 weeks before the baseline neuroendocrine tests

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Summary

Introduction

Accumulating evidence suggests that hypofunction of the mesolimbic dopamine (DA) pathway is involved in major depression, in anhedonia and loss of motivation [1,2]. Several preclinical studies have shown that chronic treatment with different classes of antidepressant drugs may increase the functional responsiveness and binding of DAD2/3 receptors in the mesolimbic system [13,14,15,16,17,18]. To deepen our understanding of the possible role of DA changes in the therapeutic response to antidepressants, functional investigations focusing on areas of the brain other than those usually studied (e.g., striatum, basal ganglia, frontal cortex, or thalamus) are needed. In this context, dynamic investigations of the hypothalamic–pituitary system—which is the primary output node for the limbic system—using DAergic agents appear relevant [25]

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