Sex-specific decision-making impairments and striatal dopaminergic changes after binge drinking history in rats

Abstract

Binge drinking (BD) is a harmful behavior for health and is a predictive factor for the development of alcohol addiction. Weak decision-making (DM) capacities could play a role in the vulnerability to BD which in turn would lead to DM impairments, thus perpetuating BD. Longitudinal preclinical studies are however lacking and necessary to understand this complex relationship. Both DM and BD are influenced by sex and involve dopamine release in the core of the nucleus accumbens, a central mechanism regulated by dopamine D2/3 autoreceptors. In this context, we used an operant self-administration procedure of BD in male and female rats, and longitudinally assessed DM capacity, memory and anxiety-like behavior. To better understand the mechanisms potentially involved in the relationship between DM and BD, ex vivo dopamine transmission was assessed short term after the end of the binge exposure in the core of the nucleus accumbens (NAc) using the fast-scan cyclic voltammetry (FSCV) technique and the D2/3 agonist quinpirole. We found important basal sex differences in DM, with female rats showing better performances at baseline. Choice processes were impaired exclusively in males after BD history, associated with a decrease in impulse control in both sexes, while memory and anxiety-like behavior were not affected. Our neurobiological results demonstrate that BD did not affect basal dopamine signaling in the NAc core, regardless of the sex, but reveal changes in the sensitivity to the inhibitory effects of quinpirole in females. DM impairments were neither associated with changes in basal dopamine signaling nor pre-synaptic D2 activity. Overall, our findings show that BD affects both DM processes and dopamine transmission in the core of the NAc in a sex-related manner, further suggesting that these effects may play a role in the vicious cycle leading to BD perpetuation and the early onset of AUD. Our results may inform novel strategies for therapeutic and prevention interventions.

Repeated Cocaine Intake Differentially Impacts Striatal D2/3 Receptor Availability, Psychostimulant-Induced Dopamine Release, and Trait Behavioral Markers of Drug Abuse

“…Studies performed in rodents to disambiguate whether impulsivity and novelty-seeking are causes or consequences of drug abuse have produced mixed results. Rats with high impulsivity, as identified by enhanced premature responding during behavioral inhibition tasks, exhibit increased rates of cocaine [16,17], nicotine [18], and alcohol [19] self-administration (SA), indicating that impulsive actions predics drug intake, although other studies failed to replicate this finding [20][21][22][23][24]. Moreover, the effect of drug exposure on impulsive action in rodents is unclear, with some studies showing either no alteration [25][26][27] or a worsening [24,[28][29][30] in impulsivity.…”

“…Rats with high impulsivity, as identified by enhanced premature responding during behavioral inhibition tasks, exhibit increased rates of cocaine [16,17], nicotine [18], and alcohol [19] self-administration (SA), indicating that impulsive actions predics drug intake, although other studies failed to replicate this finding [20][21][22][23][24]. Moreover, the effect of drug exposure on impulsive action in rodents is unclear, with some studies showing either no alteration [25][26][27] or a worsening [24,[28][29][30] in impulsivity. Intriguingly, some data suggest that the effect of drug intake on impulsive action may be baseline-dependent.…”

Greater inhibition of female rat binge alcohol intake by adrenergic receptor blockers using a novel Two-Shot rat binge drinking model

“…Our goal was to develop a BD model in outbred rats to facilitate the identi cation of individual and sex differences in drive for alcohol. It is important to note that others have developed useful binge operant intake models in rats 5 , which can have sex differences in their impact 19,20 . While there is some consideration of which rat strain might be optimal for BD studies 44 , as discussed by Sauton and colleagues 44 , rats of a given strain can differ among vendors, complicating identi cation of an widely usable optimal model.…”

“…During the past years, considerable advances were made using forced administration of alcohol through alcohol vapor, gavage, or liquid diet methods, and by studying strains with a genetic predisposition to alcohol (reviewed by Jeanblanc and colleagues 5 ). In addition, hybrid operant models have provided useful BD paradigms in rats 5 including sex differences 19,20 . Thus, we sought to develop a technically simple BD model using alcohol consumed from the bottle 21 , with the goal of setting a foundation to better understand individual and sex differences in underlying mechanisms, including where rats generally allow broader behavioral investigations.…”

Greater inhibition of female rat binge alcohol intake by adrenergic receptor blockers using a novel Two-Shot rat binge drinking model

“…During the past years, considerable advances were made using forced administration of alcohol through alcohol vapor, gavage, or liquid diet methods, and by studying strains with a genetic predisposition to alcohol (reviewed by Jeanblanc and colleagues 5 ). In addition, hybrid operant models have provided useful BD paradigms in rats 5 including sex differences 19 , 20 . Thus, we sought to develop a technically simple BD model using alcohol consumed from the bottle 21 , with the goal of setting a foundation to better understand individual and sex differences in underlying mechanisms, including where rats generally allow broader behavioral investigations.…”