title: Differential expression of CART in feeding and reward circuits in binge eating rat model.
abstract: Binge eating (BE) disrupts feeding and subverts reward mechanism. Since cocaine- and amphetamine-regulated transcript peptide (CART) mediates satiety as well as reward, its role in BE justifies investigation. To induce BE, rats were provided restricted access to high fat sweet palatable diet (HFSPD) for a period of 4 weeks. Immunoreactivity profile of the CART elements, and accompanying neuroplastic changes were studied in satiety- and reward-regulating brain nuclei. Further, we investigated the effects of CART, CART-antibody or rimonabant on the intake of normal chow or HFSPD. Rats fed on HFSPD showed development of BE-like phenotype as reflected by significant consumption of HFSPD in short time frame, suggestive of dysregulated satiety mechanisms. At the mid-point during BE, CART-immunoreactivity was significantly increased in hypothalamic arcuate (ARC), lateral (LH), nucleus accumbens shell (AcbSh) and paraventricular nucleus of thalamus (PVT). However, for next 22-h post-binge time-period, the animals showed no interest in food, and low CART expression. Pre-binge treatment with rimonabant, a drug recommended for the treatment of BE, produced anorexia, increased CART expression in ARC and LH, but not in AcbSh and PVT. Higher dose of CART was required to produce anorexia in binged rats. While neuronal tracing studies confirmed CART fiber connectivity from ARC and LH to AcbSh, increase in CART and synaptophysin immunostaining in this pathway in BE rats suggested strengthening of the CART connectivity. We conclude that CART bearing ARC-LH-PVT-AcbSh reward circuit may override the satiety signaling in ARC-PVN pathway in BE rats.
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, India.
authors.forename: Ashish P
authors.initials: AP
authors.lastname: Bharne
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, India.
authors.forename: Chandrashekhar D
authors.initials: CD
authors.lastname: Borkar
authors.affiliation: Indian Institute of Science Education and Research (IISER), Dr. Homi Bhabha Road, Pune 411008, India.
authors.forename: Nishikant K
authors.initials: NK
authors.lastname: Subhedar
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440033, India. Electronic address: kokaredada@yahoo.com.
authors.forename: Dadasaheb M
authors.initials: DM
authors.lastname: Kokare
mesh_terms: D059445:Anhedonia / Q000187:drug effects / Q000502:physiology; D000818:Animals; D056912:Binge-Eating Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D017208:Rats, Wistar; D012201:Reward; D000077285:Rimonabant; D012527:Satiation / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D063387:Cannabinoid Receptor Antagonists; D009419:Nerve Tissue Proteins; D010880:Piperidines; D011720:Pyrazoles; D016708:Synaptophysin; C569016:Syp protein, rat; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000077285:Rimonabant
keywords: Binge eating; Cocaine- and amphetamine-regulated transcript peptide (CART); Immunoreactivity; Neuroplasticity; Reward; Satiety