Orexigenic effect of cocaine- and amphetamine-regulated transcript (CART) after injection into hypothalamic nuclei in streptozotocin-diabetic rats.
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 determined using radioimmunoassays (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) increased 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.
Hou
Jun
J
Base for Drug Clinical Trail, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Zheng
De-Zhi
DZ
Zhou
Ji-Yin
JY
Zhou
Shi-Wen
SW
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein