No 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.

No abstract

This study employs an oral operant conditioning paradigm to evaluate the effects of repeated social defeat during adolescence on the reinforcing and motivational actions of ethanol in adult OF1 mice. Social interaction, emotional and cognitive behavioral aspects were also analyzed, and real-time polymerase chain reaction (PCR) experiments were performed to study gene expression changes in the mesocorticolimbic and hypothalamus-hypophysis-adrenal (HHA) axis. Social defeat did not alter anxiety-like behavior in the elevated plus maze or cognitive performance in the passive avoidance and Hebb-Williams tests. A social interaction test revealed depression-like symptoms and social subordination behavior in defeated OF1 mice. Interestingly, social defeat in adolescence significantly increased the number of effective responses, ethanol consumption values and motivation to drink. Finally, real-time PCR analyses revealed that social defeat significantly increased tyrosine hydroxylase and corticotropin-releasing hormone in the ventral tegmental area and paraventricular nucleus, respectively. In contrast, mu-opioid receptor gene expression was decreased in the nucleus accumbens of socially defeated mice. In summary, these findings suggest that exposure to social defeat during adolescence increases vulnerability to the rewarding effects of ethanol without affecting emotional or cognitive performance. The gene expression alterations we have observed in the mesocorticolimbic and HHA axis systems of defeated mice could be related with their increased ethanol consumption. These results endorse future research into pharmacological strategies that modulate these systems for the treatment of social stress-related alcohol consumption problems.

No abstract

Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.

Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of social defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the social defeat stress model, and will discuss challenges and future directions.

Our results suggest that CB2r is implicated in social interaction and aggressive behavior and deserves further consideration as a potential new target for the management of aggression.