Department News
PI Researchers Report HPA Axis Abnormalities in Alcoholism

In the current issue of the Journal of Pharmacology and Experimental Therapeutics, Psychiatric Institute investigators make the first report of a molecular basis for disturbed HPA axis in alcholism. The Hypothalamic-pituitary Adrenal (HPA) axis is one of the primary physiological systems activated during alcohol exposure and it plays an important role in the harmful effects of alcohol on neuronal functions. Subhash Pandey, Ph.D., and his colleagues, Adip Roy, Ph.D., Navadha Mittal, Ph.D. and Huaibo Zhang, Ph.D., observed novel mechanisms which suggest that decreased protein expression of glucocorticoid receptors (GR) in the neural circuitry of paraventricular nucleus (PVN) of hypothalamus may contribute to hyperactive HPA axis during chronic ethanol exposure and its withdrawal in rats. Mianserin (5-HT2A/2C receptor antagonist) treatment prevented the ethanol-induced reductions in GR protein expression in various neurocircuitry such as hypothalamus, cortex, and amygdala but not in hippocampus. These results provide the first molecular basis for disturbed HPA axis in alcoholism. "If we find that other serotonergic antidepressant drugs produce the same effects, it would suggest the possibility that serotonergic antidepressant drugs may be beneficial in preventing alcohol-induced changes in HPA axis in alcoholics," Dr. Pandey said. The article is in volume 301, pages 774-784.