Abstract

Introduction: Anxiety and negative sensations due to alcohol withdrawal are factors leading to alcohol relapse and addiction. Minocycline, an antibiotic, can decrease alcohol consumption in rats, however, its effects on alcohol withdrawal anxiety and relapse have not been studied.

Material and Methods: Part 1: Forced alcohol drinking in gradually increasing concentration was administered till day 22 in rats. Effect of drugs on anxiety was assessed using elevated plus maze (EPM) and two-chambered box apparatus, after removal of alcohol. Part 2: For relapse, an alcohol deprivation effect model was used, rats were continuously offered alcohol and water for 4 consecutive weeks in a two-bottle choice paradigm, followed by 2 weeks of alcohol deprivation. Effect of drugs on alcohol consumption during the first hour of alcohol reintroduction was assessed. Animals were sacrificed and whole brain Tumor Necrosis Factor (TNF) α was estimated.

Results: Part 1: Anxiety at 3 hours was significantly lower following minocycline (20 mg/kg i.p.) or diazepam compared to vehicle control. Part 2: Acute administration of minocycline (5,10 and 20 mg/kg, i.p.) suppressed alcohol consumption significantly (p value<0.05) as compared to vehicle control. A significant decrease in whole brain TNF α was observed in animals treated with minocycline compared to untreated animals.

Conclusion: Minocycline attenuates alcohol withdrawal anxiety and disrupts alcohol relapse.

Keywords: Elevated plus maze, two-chambered box, alcohol deprivation effect, alcohol withdrawal anxiety.

Graphical Abstract