Mirtazapine acutely inhibits basal and K+-stimulated release of corticotropin-releasing hormone from the rat hypothalamus via a non-genomic mechanism

Abstract

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. 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. 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. 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.

DOI: 10.1007/s00213-004-1984-6

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@article{Fabrcio2004MirtazapineAI, title={Mirtazapine acutely inhibits basal and K+-stimulated release of corticotropin-releasing hormone from the rat hypothalamus via a non-genomic mechanism}, author={Aline Sueli Coelho Fabr{\'i}cio and Giuseppe Tringali and Giacomo Pozzoli and Pierluigi Navarra}, journal={Psychopharmacology}, year={2004}, volume={178}, pages={78-82} }