1. Hypothalamic cocaine- and amphetamine-regulated transcript peptide is reduced and fails to modulate feeding behavior in rats with chemically-induced mammary carcinogenesis.
- Author
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Nakhate KT, Kokare DM, Singru PS, Taksande AG, Kotwal SD, and Subhedar NK
- Subjects
- Animals, Anorexia etiology, Anorexia psychology, Antibody Specificity, Blood Glucose metabolism, Blood Proteins metabolism, Body Weight drug effects, Cachexia prevention & control, Carcinogens, Cholesterol blood, Eating drug effects, Female, Hypothalamus drug effects, Hypothalamus physiology, Immunohistochemistry, Infusions, Intraventricular, Methylnitrosourea, Nerve Tissue Proteins immunology, Rats, Rats, Sprague-Dawley, Triglycerides blood, Cocaine- and Amphetamine-Regulated Transcript Protein, Feeding Behavior physiology, Hypothalamus metabolism, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental psychology, Nerve Tissue Proteins metabolism
- Abstract
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 5days, 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., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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