Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system

Abstract

Objective: Although hyperphagia and body weight gain are well-recognized consequences of social isolation, the underlying mechanisms are not understood. The aim of this work is to test the possibility that the endogenous cocaine-and amphetamineregulated transcript peptide (CART) may be involved in the process. Design: Socially isolated rats were screened for increase in food intake and body weight, and the modifications of these parameters by CART were evaluated. Furthermore, isolated animals were re-socialized and screened for reversal of these effects. Response of the endogenous CART system, in certain hypothalamic nuclei of the isolated and re-socialized rats, was evaluated with immunohistochemistry. Subjects: Fifty days old naive male Sprague-Dawley rats were used. Measurements: The effects of CART/CART antibody on the social isolation and subsequent re-socialization on feeding and body weight changes were monitored. Moreover, the immunohistochemical response of endogenous CART system to social isolation and re-socialization was analyzed morphometrically. Results: While social isolation of rats for a period of 6 weeks caused progressive increase in food consumption and body weight gain, these rats showed a significant reduction in food intake and body weight when injected daily with CART via intracerebroventricular (i.c.v.) route, for the following 7 days. The re-socialization of isolated rats reduced food intake and body weight to the control levels. These effects of re-socialization were attenuated by immunoneutralization of the endogenous CART by i.c.v. CART antibody. Social isolation also resulted in a drastic reduction in CART immunoreactivity in the cells and/or fibers in the hypothalamic areas like dorsomedial, ventromedial, lateral, paraventricular and arcuate nuclei, recognized for their role in feeding. On the other hand, the CART immunoreactivity profile was fully restored following 7 days of re-socialization of the isolation-reared rats. Conclusion: Social isolation might down-regulate the hypothalamic CART-containing system, which in turn may lead to increase in food intake and body weight.

Differential expression of CART in feeding and reward circuits in binge eating rat model

“…Icv administration of 0.5 or 1 g of CART produced significant reduction in food intake in normal rats [14,26] as also observed in the present study. However, in binged rats, twice the dose of CART was required to produce similar degree of reduction in HFSPD intake.…”

“…Omission of the primary antibody and replacement with BSA produced no synaptophysin immunoreaction. In preadsorption controls, application of diluted antibody pre-incubated with CART at 10 −5 M for 24-h, completely blocked the CART-immunoreaction [26].…”

“…The procedure for the stereotaxic cannulation of rat, and postsurgical care has been standardized in our laboratory [26]. A stainless steel guide cannula (24 gauge), fabricated in-house [27], was implanted into the right lateral cerebral ventricle using the stereotaxic coordinates, −0.8 mm posterior, +1.3 mm lateral to midline and 3.5 mm ventral with respect to bregma as per the stereotaxic atlas [28].…”

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

“…CART protein is encoded by the CARTPT gene, which functions in feeding, reward, stress and pain transmissions [152,153]. Similar to POMC, CART also downregulates food intake and body weight [154,155]; a previous study revealed that CART has an effect on neuronal activities (including the hypothalamic VMH and PVN), which are involved in the neuroplasticity of hypothalamic feeding circuits [156].…”

Binge-Eating Behavior in Socially-Insolated Female Mice

“…This is consistent with literature demonstrating that social isolation can modify feeding habit without changing body weight. In rats, 6 but not 3 weeks of isolation increased bodyweight though both increased weekly food intake (Nakhate, Kokare, Singru, & Subhedar, 2011;Perez et al, 1997). In mice, neither 2 nor 8 weeks of isolation changed body weight in adult mice despite altering feeding (Sun et al, 2014;Yamada et al, 2015).…”