A few days ago, my first, first author paper was finally published in Alcoholism: Clinical and Experimental Research. After spending years working on the project, months writing and re-writing the paper, and another few months swearing at Adobe Photoshop for its stubborness, the journey has been captured in eight pages. Here, I describe the results, relying on my schematics of which most of my family will do as well.
First, I wanted to characterize circadian alcohol consumption (how much and what time of the day does drinking occur) in our wild-type mouse strain, which have a moderate preference for alcohol and therefore, requires little training to get them to drink. To do this, I implanted the animals with a probe in their circadian clock that could reliably measure alcohol uptake and the time of uptake within the clock.
As shown, most of the drinking occurred soon after the animals woke up (bloody marys!!) and right before bedtime (gin and tonics!!!) with sometimes, a drinking bout here and there in the middle of the sleeping period (left over bloody marys or gin and tonics!!!).
Once I had an idea of their circadian alcohol consumption, I then presented the animals with a light pulse during their nocturnal activity period, knowing that this pulse would delay their subsequent sleep/wake rhythms (i.e. they would reliably wake up 1.5-2 hrs later the following few days).
Here, we see that daily, chronic alcohol consumption and its withdrawal reduced the animal’s responsiveness to this light cue, with the effect being more pronounced in animals consuming the more concentrated alcohol solution.
Finally, I conducted a few long-term (13 months ) behavioral experiments addressing the effects of alcohol on their general circadian behavioral rhythms under a more natural environmental schedule (these animals are burrowers and don’t see sunlight across all hours of the day), yet unusual laboratory schedule. To do this, I began with a regular laboratory schedule of 12 hours of light and dark followed by the more natural environmental schedule of 23.99 hours of constant dark with a 1 min light pulse presented in the middle of the animals usual rest period. This type of schedule would force the animals to re-entrain their behavioral rhythms towards the light pulse and therefore , I could assess if alcohol would affect this rate of re-entrainment. It didn’t as shown here, but it definitely disrupted daily circadian locomotor rhythms by reducing the amount of activity across the nocturnal activity period (perhaps to drunk to move)?
What’s the significance of this research? First, it demonstrates that alcohol and its withdrawal directly disrupts circadian physiology which in the long-term may drive alcohol addiction; eliciting difficulty falling asleep, resulting in a reliance on alcohol as a hypnotic,and a subsequent alcohol-disruption of sleep, leading to more alcohol consumption to fall asleep the following night. Second, it illustrates how robust the circadian clock is across species given that alcohol elicits similar impairing circadian effects as reported via self-reports in humans. This indicates that murine and other rodent models are ideal for investigating the neural mechanisms of alcohol dispruption on the mammalian circadian clock and developing novel chronotherapeutic (manipulating sleep/wake schedules, perhaps even functionality of the circadian clock itself) for the treatment of alcoholism.
Brager AJ, Ruby CL, Prosser RA, & Glass JD (2010). Chronic Ethanol Disrupts Circadian Photic Entrainment and Daily Locomotor Activity in the Mouse. Alcoholism, clinical and experimental research PMID: 20477766