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Alcohol and Alcoholism Vol. 36, No. 1, pp. 59-64, 2001
© 2001 Medical Council on Alcoholism

Acetaldehyde, a metabolite of ethanol, activates the hypothalamic–pituitary–adrenal axis in the rat

Hiroshi Kinoshita, David S. Jessop, David P. Finn, Toni L. Coventry, David J. Roberts1, Kiyoshi Ameno2, Iwao Jiri2 and Michael S. Harbuz*

URC for Neuroendocrinology, University of Bristol, BRI, Marlborough Street, Bristol BS2 8HW,
1 School of Chemistry, University of Bristol, Cantocks Close, Bristol BS8 1TS, UK and
2 Department of Forensic Medicine, Kagawa Medical University, 1750-1, Miki, Kita, Kagawa, 761-0793, Japan

Received 20 July 2000; first review notified 18 August 2000; accepted 22 August 2000

— Cyanamide is a potent inhibitor of aldehyde dehydrogenase (ALDH: EC 1.2.1.3) used in the treatment of alcoholics. In the presence of ethanol, cyanamide causes an accumulation of acetaldehyde, a highly toxic metabolite of ethanol, with unpleasant side-effects. A similar accumulation is seen in some Oriental people with low ALDH activity. We have investigated the effects of ethanol and cyanamide administration on the activation of the hypothalamic–pituitary–adrenal (HPA) axis using in situ hybridization histochemistry and radioimmunoassay. Ethanol plus cyanamide resulted in a significant increase in corticotrophin-releasing factor and arginine vasopressin mRNA in the paraventricular nucleus, and pro-opiomelanocortin mRNA in the anterior pituitary. Plasma corticosterone concentrations were also significantly elevated following ethanol plus cyanamide administration. The blood concentration of acetaldehyde in the ethanol plus cyanamide group increased significantly. These results suggest that acetaldehyde, induced by blocking ethanol metabolism, is able to activate the HPA axis operating through a central mechanism.


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