Hypothalamic cocaine- and amphetamine-regulated transcript peptide is reduced and fails to modulate feeding behavior in rats with chemically-induced mammary carcinogenesis.
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.
Nakhate
Kartik T
KT
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, Maharashtra, 440 033, India.
Kokare
Dadasaheb M
DM
Singru
Praful S
PS
Taksande
Amit G
AG
Kotwal
Swati D
SD
Subhedar
Nishikant K
NK
D000818:Animals; D000855:Anorexia / Q000209:etiology / Q000523:psychology; D000918:Antibody Specificity; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000517:prevention & control; D002273:Carcinogens; D002784:Cholesterol / Q000097:blood; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D057967:Infusions, Intraventricular; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000523:psychology*; D008770:Methylnitrosourea; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D001786:Blood Glucose; D001798:Blood Proteins; D002273:Carcinogens; D009419:Nerve Tissue Proteins; D014280:Triglycerides; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D008770:Methylnitrosourea; D002784:Cholesterol