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


OBJECTIVE
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.


CONCLUSIONS
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.
Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, 00168, Rome, Italy.
Aline S C
AS
Fabricio
Giuseppe
G
Tringali
Giacomo
G
Pozzoli
Pierluigi
P
Navarra
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078785:Mirtazapine; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D011189:Potassium Chloride; D003346:Corticotropin-Releasing Hormone; D000078785:Mirtazapine