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

TL;DR

A new rat model for binge drinking shows that female rats are more responsive to adrenergic drugs, suggesting potential sex-specific treatments for alcohol use disorder.

Contribution

A novel Two-Shot binge drinking model in outbred rats reveals sex differences in adrenergic receptor blockade effects on binge alcohol intake.

Findings

Female rats showed reduced binge drinking with propranolol and prazosin at lower doses, unlike males.

The Two-Shot model reliably achieves binge-level BACs in outbred rats.

Alcohol intake was suppressed by naltrexone, confirming its therapeutic relevance in the model.

Abstract

Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-minute intake (what we called Two-shot) separated by a 10-minute break. Our findings showed during Two-Shot that most animals reached ≥ 80mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20% to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1mg/kg), validating intake suppression by a clinical therapeutic agent. Further, both propranolol (β adrenergic receptor antagonist) and prazosin (α1 adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.

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