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Epinephrine: A Short- and Long-Term Regulator of Stress and Development of Illness

A Potential New Role for Epinephrine in Stress

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Abstract

Epinephrine (Epi), which initiates short-term responses to cope with stress, is, in part, stress-regulated via genetic control of its biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT). In rats, immobilization (IMMO) stress activates the PNMT gene in the adrenal medulla via Egr-1 and Sp1 induction. Yet, elevated Epi induced by acute and chronic stress is associated with stress induced, chronic illnesses of cardiovascular, immune, cancerous, and behavioral etiologies. Major sources of Epi include the adrenal medulla and brainstem. Although catecholamines do not cross the blood–brain barrier, circulating Epi from the adrenal medulla may communicate with the central nervous system and stress circuitry by activating vagal nerve β-adrenergic receptors to release norepinephrine, which could then stimulate release of the same from the nucleus tractus solitarius and locus coeruleus. In turn, the basal lateral amygdala (BLA) may activate to stimulate afferents to the hypothalamus, neocortex, hippocampus, caudate nucleus, and other brain regions sequentially. Recently, we have shown that repeated IMMO or force swim stress may evoke stress resiliency, as suggested by changes in expression and extinction of fear memory in the fear-potentiated startle paradigm. However, concomitant adrenergic changes seem stressor dependent. Present studies aim to identify stressful conditions that elicit stress resiliency versus stress sensitivity, with the goal of developing a model to investigate the potential role of Epi in stress-associated illness. If chronic Epi over expression does elicit illness, possibilities for alternative therapeutics exist through regulating stress-induced Epi expression, adrenergic receptor function and/or corticosteroid effects on Epi, adrenergic receptors and the stress axis.

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Acknowledgments

This study was supported by The Spunk Fund, Inc., the Sobel-Keller Research Fund, McLean Hospital, and the Emerald Foundation, Inc. (DLW), NSERC and CIHR grants (TCT), MH063266 (WAC) and Slovak Grants, APVV-0088-10 and VEGA 2/0036-11 and 2/0188-09 (RK).

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Authors and Affiliations

  1. Department of Psychiatry, Harvard Medical School and Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, 115 Mill Street, MRC Rm 116, Mail Stop 144, Belmont, MA, 02478, USA

    Dona Lee Wong, T. C. Tai, David C. Wong-Faull & Robert Claycomb

  2. Division of Medical Sciences, Northern Ontario School of Medicine, Laurentian University, Sudbury, ON, P3E 2C6, Canada

    T. C. Tai

  3. Department of Psychiatry, Harvard Medical School and Behavioral Genetics Laboratory, McLean Hospital, Belmont, MA, 02478, USA

    Edward G. Meloni, Karyn M. Myers & William A. Carlezon Jr.

  4. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia

    Richard Kvetnansky

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  1. Dona Lee Wong
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  2. T. C. Tai
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  3. David C. Wong-Faull
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Correspondence to Dona Lee Wong.

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Wong, D.L., Tai, T.C., Wong-Faull, D.C. et al. Epinephrine: A Short- and Long-Term Regulator of Stress and Development of Illness. Cell Mol Neurobiol 32, 737–748 (2012). https://doi.org/10.1007/s10571-011-9768-0

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