| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2013164 | Pharmacology Biochemistry and Behavior | 2010 | 10 Pages |
Cocaine- and amphetamine-regulated transcript peptide (CART) is a major anorectic agent present in the hypothalamus. We investigated the possible role of CART in mammary cancer-induced anorexia and body weight loss in rats. Mammary carcinogenesis was induced in the female Sprague-Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Following administration of MNU, rats progressively showed a reduction in food intake and body weight. Fourteen weeks after MNU treatment, rats were injected daily with CART or CART-antibody intracerebroventricularly for 5Â days, and food intake and body weight were monitored (g) before the next injection time-point. In normal rats, while a distinct anorexia and weight loss was observed following CART administration, injection of CART-antibody produced opposite effects. However, both the agents failed to produce any significant alterations in food intake and body weight of mammary tumor-bearing animals. An immunohistochemical application of antibodies against CART to the brain sections of cancerous rats showed a reduced immunoreactivity in the hypothalamic dorsomedial, ventromedial, lateral, paraventricular and arcuate nuclei. The results suggest that, cancerous condition might down-regulate the CART system in the hypothalamus. Alternatively, reduction in hypothalamic CART activity might be a counter-regulatory strategy to reverse food under-consumption or body mass erosion.
Research HighlightsâºMammary cancer accompanies cachexia (anorexia and weight loss). âºCachexia leads to a state of negative energy balance. âºNegative energy state down-regulates hypothalamic anorectic CART system. âºReduced CART may be an attempt to restore an energy balance or to reverse cachexia.
