Transient up-regulation of cocaine- and amphetamine-regulated transcript peptide (CART) immunoreactivity following ethanol withdrawal in rat hypothalamus

We investigated the profile of CART immunoreactivity in some discrete hypothalamic nuclei following chronic ethanol treatment and withdrawal conditions. Adult, male, Sprague-Dawley rats were fed with liquid diet (pair-fed) or liquid diet containing ethanol (ethanol-fed) for 15 days. Thereafter, all the animals were given access to ethanol free nutritionally balanced liquid diet and killed at 0, 24, 48 and 72 h post-withdrawal, and their brains processed for immunocytochemistry using monoclonal antibodies against CART. CART-immunoreactive fibers, but not the cells, were significantly increased in the paraventricular nucleus (PVN). However, the profile of CART-immunoreactive cells and/or fibers in the periventricular area (PeA), arcuate nucleus (ARC), perifornical area inclusive of lateral hypothalamus (LH) and tuber cinereum (TC), dorsomedial (DMH), and ventromedial (VMH) hypothalamus at the 0 h ethanol withdrawal time point was quite similar to that in the pair-fed control rats. Twenty-four hours following ethanol withdrawal, the immunoreactivity in all these areas was dramatically increased. While significant reduction in CART immunoreactivity was noticed in the PVN, PeA, ARC and VMH at 48 h, immunoreactive profile was restored to normal by 72 h post-ethanol withdrawal. The immunoreactive profile in the LH, TC and DMH resembled that of the pair-fed groups at 48 and 72 h post-withdrawal intervals. However, CART-immunoreactive profile in the supraoptic nucleus did not respond to the chronic ethanol treatment and/or withdrawal. We suggest that transient up-regulation of CART in some discrete hypothalamic nuclei following ethanol withdrawal, at least in part, may contribute to the pathogenesis of ethanol withdrawal-induced symptoms like anxiety and anorexia. (C) 2008 Elsevier B.V. All rights reserved.