Abstract
Alcohol use is one of the world’s leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption.
Highlights
Alcohol use disorder, which includes the spectrum of drinking behaviors and consequences ranging from risky use to heavy dependence, has been linked to a wide array of health and social problems[1]
Taking cue from past observations inspired by clinical experience[34], we report here a novel animal model addressing alcohol use disorder
At the end of the baseline self-administration period (80 sessions during which animals were trained under a fixed ratio 1, time out 4 sec to get 0.1 mL of 10% w/v ethanol, see Fig. 1), rats underwent a procedure for screening evidence for addiction-like behavior[35]
Summary
Alcohol use disorder, which includes the spectrum of drinking behaviors and consequences ranging from risky use to heavy dependence, has been linked to a wide array of health and social problems[1]. With one core symptom of drug addiction being the high risk of relapse after a period of abstinence, the extinction/reinstatement model has long been used for assessing the neurobiological mechanisms underlying drug seeking behaviors[17,18,19] with the aim of screening effective drug treatments to prevent relapsing behaviors One limitation of this approach is the lack of consideration for individual vulnerability since all subjects are treated with similar drug doses to assess the pharmacological impact of those drugs to prevent cue-, stress- or priming-induced reinstatement of drug seeking behaviors[20]. This approach revealed a large spectrum of severity for cocaine abuse in rats, but it allowed to better depict the neurobiological adaptations occurring in the brain of rats developing the behavioral hallmarks of cocaine addiction[35,36,37,38,39,40,41,42]
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