Abstract
Rationale
Originally described as a pivotal mediator of acute neuroendocrine responses to stress, corticotropin-releasing hormone (CRH) is currently envisioned as a peptide neurotransmitter involved in the pathogenesis of anxiety and depressive disorders; it has been postulated that antidepressant drugs are clinically effective insofar as they are able to reduce central CRH production and release.
Objectives and methods
In this study we used a well validated in vitro model, i.e. acute rat hypothalamic explants, to investigate the effects of the antidepressant mirtazapine on the production and release of CRH from the hypothalamus in short-term experiments. CRH release was assessed through the measurement of CRH immunoreactivity in the incubation medium.
Results
We found that mirtazapine reduces in a concentration-dependent manner both basal and K+-stimulated CRH release in 30-min and 60-min experiments. Mirtazapine had no effect on CRH mRNA expression in 1-h and 3-h experiments; the intra-hypothalamic levels of peptide were not reduced, and even tended to increase, with respect to controls.
Conclusion
Mirtazapine reduces CRH release from CRH-containing neurons in the rat hypothalamus through a mechanism independent from the modulation of CRH gene expression and peptide production.
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This work was supported by Organon Italia S.p.A.
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Fabricio, A.S.C., Tringali, G., Pozzoli, G. et al. Mirtazapine acutely inhibits basal and K+-stimulated release of corticotropin-releasing hormone from the rat hypothalamus via a non-genomic mechanism. Psychopharmacology 178, 78–82 (2005). https://doi.org/10.1007/s00213-004-1984-6
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DOI: https://doi.org/10.1007/s00213-004-1984-6