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

Abstract

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.

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

“…63 Moreover, two studies found that mice or rats intermittently and time-limited fed with a palatable diet over several weeks displayed a reduction of plasma ghrelin levels immediately after the last binge eating event. 64,65 Other studies, however, could not confirm these observations and found that rats time-limited fed with palatable diets, either daily or intermittently, over several weeks did not change plasma ghrelin levels in anticipation to the scheduled meals compared to control rats. 50,66 Also, another study found that female rats with daily and limited access to a palatable diet over several weeks displayed lower plasma ghrelin levels under fasting compared to control rats.…”

“…In particular, one study found that increments of plasma ghrelin levels positively correlated with food anticipatory activity and that a GHSR antagonist decreased such behaviour, whereas another study showed that blockade of plasma ghrelin increments attenuated the magnitude of binge‐like HF intake . Moreover, two studies found that mice or rats intermittently and time‐limited fed with a palatable diet over several weeks displayed a reduction of plasma ghrelin levels immediately after the last binge eating event . Other studies, however, could not confirm these observations and found that rats time‐limited fed with palatable diets, either daily or intermittently, over several weeks did not change plasma ghrelin levels in anticipation to the scheduled meals compared to control rats .…”

Social defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse

“…Drug use during this critical period of development often predisposes to an increased likelihood of continued use into adulthood (Arteaga, Chen, & Reynolds, ). Moreover, social (e.g., peer influence), economic (e.g., low social status), hormonal (increase in adrenal and gonadal hormones), neurochemical (changes in DA neurotransmission) and dietary (high‐fat/sugar diets) conditions during adolescence also contribute to increased vulnerability to drug use (Blanco‐Gandía, Cantacorps et al., , Blanco‐Gandía, Ledesma et al., ; Spear, ). Social stress in early life, such as bullying at school or child abuse, can have several consequences in adulthood (de Groot, van Milligen, Moonen‐Leusen, Thomas, & Koolhaas, ; Lumley, Sipos, Charles, Charles, & Meyerhoff, ).…”

Increased ethanol consumption after interruption of fat bingeing

“…Nevertheless, it has been proposed that binge-eating, as a maladaptive behavior, could work as a gateway for the development of drug addiction [ 30 – 33 ]. We have recently confirmed that bingeing on fat increases cocaine and EtOH consumption and the conditioned rewarding effects of both drugs [ 32 , 33 ]. First, we demonstrated that animals bingeing on fat were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the conditioned place preference and presented enhanced cocaine self-administration.…”