Hypothalamic cocaine- and amphetamine-regulated transcript peptide is reduced and fails to modulate feeding behavior in rats with chemically-induced mammary carcinogenesis

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• 作者：Kartik T. Nakhate ; Dadasaheb M. Kokare ; Praful S. Singru ; Amit G. Taks ; e ; Swati D. Kotwal ; Nishikant K. Subhedar
• 关键词：Breast cancer ; Cocaine- and amphetamine-regulated transcript ; Hypothalamus ; N-methyl-N-nitrosourea ; Food intake ; Body weight
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：97
• 期：2
• 页码：340-349
• 全文大小：1744 K

文摘

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 5 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.