Rapid Tolerance Development to the NREM Sleep Promoting Effect of Alcohol

Study Objectives: Alcohol tolerance is a major contributor towards the development of alcohol dependence. Does alcohol intake result in rapid tolerance development to alcohol induced NREM sleep promotion? This has never been examined. Our objective was to examine whether two bouts of alcohol consumption on consecutive days results in rapid tolerance development to alcohol-induced NREM sleep promotion. Design: N/A. Setting: N/A. Patients or Participants: C57BL/6J mice. Interventions: Mice (N = 5) were implanted with sleep electrodes using standard surgical conditions. Following postoperative recovery and habituation, the experiment was begun. On baseline day, water bottle changes were performed at 10: 00 (3 h after dark onset) and 14: 00 to mimic conditions during alcohol consumption days. On next 2 days, (Days 1 and 2) mice were allowed to self-administer alcohol (20% v/v) for 4 h beginning at 10: 00 and ending at 14: 00. Sleep-wakefulness was continuously recorded from 10: 00 to 18: 00 (8 h; 4 h during alcohol + 4 h post-alcohol) on all 3 days. Measurements and Results: Although mice consumed comparable amounts of alcohol on Days 1 and 2, NREM sleep and wakefulness were significantly and differentially affected during 4 h post-alcohol period. A robust alcohol-induced NREM sleep promotion was observed on Day 1. However, no such sleep promotion was observed on Day 2, suggesting rapid tolerance development. Conclusions: Our study is the first to demonstrate that alcohol consumption for two consecutive days results in development of rapid tolerance to alcohol-induced sleep promotion.