ALCOHOL DEPENDENCE ALTERS DISCOUNTING AND BRAIN-WIDE FUNCTIONAL CONNECTIVITY

The consumption of alcohol can evolve from controlled social use into the compulsive, relapsing disorder that characterizes alcohol use disorder (AUD). The mechanism behind this transition remains not fully understood. However, there is solid evidence that repeated intoxicating cycles of alcohol and withdrawal engender long-term alterations in gene expression and synaptic plasticity. These lead to persistent alterations in neuronal network activity, hypothesized to drive relapse and compulsive alcohol use in dependent individuals even after detoxification. Thus, identifying the altered neurobiological substrates mediating the motivational properties of relapse is an important step in the development of new treatments for AUD. A particular intriguing feature of AUD patients is the disregard of negative outcomes over the immediate gratification provided by alcohol. This suggests a rapid devaluation of future events. Many studies have focused on delay discounting of rewards, but the discounting of future negative outcomes seems to be even more relevant, since continued use despite aversive consequences is a core symptom of addiction.
Here, we examined the effects of alcohol dependence on reward and aversion discounting. To determine alterations in neural mechanisms underlying these alcohol-related decision making process, we assessed brain-wide neuronal activity and connectome using graph theoretical analysis. Results demonstrate that across both discounting paradigms involving delayed reward and delayed negative outcomes, alcohol-dependent rats exhibited an increased preference for the large reward. These behavioural effects were accompanied by significant changes in neuronal network configuration and organisation.
Targeting these dysfunctional circuits may offer new avenues for interventions aimed at preventing relapse.