Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice

Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine. After 40 days of binge-eating for 2 h, three days a week (PND 29–69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice. Circulating leptin and ghrelin levels and the effects of bingeing on fat on CB1 mu opioid receptor (MOr) and ghrelin receptor (GHSR) gene expression in the Nucleus Accumbens (NAcc) and Ventral Tegmental Area (VTA) were also assessed. Our results showed a significant escalation in the consumption of a high-fat diet between the first and last week. High-fat binge (HFB) animals were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the paradigms assayed, and animals under fat withdrawal were more vulnerable to the reinstatement of conditioned place preference. HFB mice also showed enhanced cocaine self-administration. After fat withdrawal, exposure to a new fat binge reinstated cocaine seeking. Although HFB did not modify leptin levels, a decrease in plasmatic ghrelin was observed. Moreover, this pattern of fatty diet resulted in a reduction of MOr and CB1 gene expression in the NAcc and an increase in GHSR expression in the VTA. We propose that bingeing on fat during adolescence induces long-lasting changes in the brain through the sensitization of brain reward circuits, which predisposes individuals to seek cocaine during adulthood.
This study was supported by the Spanish Ministry of Economy and Innovation and FEDER (SAF2013-41761-R; PSI2014-51847-R; and PSI2011-24762), Spanish Ministry of Health, Social Affairs and Equality (PNSD 2014-020 and 2014-I007); Instituto de Salud Carlos III, Red de Trastornos Adictivos (RTA) (RD12/0028/0005, RD12/0028/0019 and RD12/0028/0024) and Unión Europea, Fondos FEDER “una manera de hacer Europa”. Generalitat Valenciana, PROMETEOII/2014/063 and Generalitat de Catalunya (2014SGR34).