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Acute and chronic effects of the atypical antidepressant, mianserin on brain noradrenergic neurons

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Abstract

Corticotropin-releasing factor (CRF), which may serve as a neurotransmitter in the noradrenergic nucleus, locus coeruleus (LC), has been postulated to be hypersecreted in depression. The present study was designed to test the hypothesis that antidepressants interfere with CRF putative neurotransmission in the LC. The acute and chronic effects of the atypical antidepressant mianserin on LC spontaneous discharge, LC sensory-evoked discharge, LC activation by a stressor which requires endogenous CRF, and LC activation by ICV CRF were characterized in halothane-anesthetized rats. Acute IV administration of mianserin (0.0001–1.0 mg/kg) increased LC spontaneous discharge and decreased LC discharge evoked by repeated sciatic nerve stimulation in a dose-dependent manner. Additionally, mianserin (0.1 mg/kg) inhibited LC activation by hemodynamic stress (IV infusion of nitroprusside) and by ICV administration of CRF (3.0 µg). In rats chronically administered mianserin LC spontaneous and sensory-evoked discharge rates, and LC activation by CRF were similar to those of untreated rats or rats chronically administered saline. Moreover, acute IV administration of mianserin (0.1 mg/kg) to rats chronically treated with mianserin was less effective in altering LC spontaneous and sensory-evoked discharge. In contrast, LC activation by hemodynamic stress was still greatly attenuated in rats chronically administered mianserin. This is similar to the previously reported effect produced by chronic administration of the antidepressant, desmethylimipramine. The present results demonstrate that acute administration of low doses of mianserin attenuates LC activation by a variety of stimuli and suggest that tolerance developes with chronic administration to some of the effects of mianserin on LC discharge characteristics. The finding that LC activation by hemodynamic stress, which requires endogenous CRF, is attenuated after chronic mianserin administration suggests that interference with putative CRF neurotransmission in the LC may be an important common mode of antidepressant action.

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Authors and Affiliations

  1. Division of Behavioral Neurobiology, Department of Mental Health Sciences, Hahnemann University, 19102, Philadelphia, PA, USA

    Andre L. Curtis & Rita J. Valentino

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  1. Andre L. Curtis
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  2. Rita J. Valentino
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This work was supported by U.S.P.H.S. Grants MH42796, MH40008, MH00840, and a NARSAD award to A.L.C.

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Curtis, A.L., Valentino, R.J. Acute and chronic effects of the atypical antidepressant, mianserin on brain noradrenergic neurons. Psychopharmacology 103, 330–338 (1991). https://doi.org/10.1007/BF02244286

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  • DOI: https://doi.org/10.1007/BF02244286

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