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Orexigenic effect of cocaine‐ and amphetamine‐regulated transcript (CART) after injection into hypothalamic nuclei in streptozotocin‐diabetic rats
Author(s) -
Hou Jun,
Zheng DeZhi,
Zhou JiYin,
Zhou ShiWen
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05423.x
Subject(s) - orexigenic , cart , cocaine and amphetamine regulated transcript , medicine , endocrinology , hypothalamus , neuropeptide y receptor , arc (geometry) , arcuate nucleus , neuropeptide , streptozotocin , chemistry , hormone , biology , diabetes mellitus , receptor , mechanical engineering , geometry , mathematics , engineering
Summary 1. The aim of the present study was to investigate the orexigenic effect of cocaine‐ and amphetamine‐regulated transcript (CART) peptide on feeding regulation following its injection into discrete nuclei of the hypothalamus. 2. Male Sprague‐Dawley diabetic rats were injected with 0.06 or 0.2 nmol CART (55–102) or an equal volume of saline into various hypothalamic areas and food intake was then measured 1, 2, 4, 8 and 24 h after injection. Changes in hypothalamic CART mRNA expression in response to dietary intervention (2 weeks feeding of a high‐fat diet) were assessed using quantitative real‐time reverse transcription–polymerase chain reaction. Possible interactions between neuropeptide Y (NPY), agouti‐related protein (AGRP), α‐melanocyte‐stimulating hormone (MSH) and corticotropin‐releasing hormone (CRH) were evaluated in an in vitro hypothalamic explant system. Neuropeptide immunoreactivities (IR) were detertmined using radioimmunassays (RIAs). 3. At 0.2 nmol, CART (55–102) significantly increased feeding in fasted diabetic rats after injection into the dorsomedial hypothalamic nucleus and arcuate nucleus (ARC). Injection of 0.2 nmol CART (55–102) into the ARC of satiated diabetic rats also increased food intake that was similar in both magnitude and time‐course to the response seen in fasted diabetic rats. Food intake in diabetic rats on a high‐fat diet was clearly increased after injection of 0.2 nmol CART (55–102) into the ARC, as was CART mRNA expression. Incubation of hypothalamic explants with 0.4, 4 and 40 nmol/L CART (55–102) for 45 min significantly increased NPY IR, whereas exposure of explants to 4 nmol/L CART (55–102) increaesd AGRP IR and CRH IR. None of the concentrations of CART (55–102) tested had any effect on α‐MSH IR. 4. Together, these data provide further evidence that hypothalamic CART has an orexigenic effect, which, in the ARC, may stimulate the release of hypothalamic orexigenic neuropeptides.