Though these experiments were completed ages ago (about 2 years, this summer), the work has finally been published in Alcoholism: Clinical and Experimental Research. These data are an extension and in agreement with what we found under conditions of chronic ethanol intake, which would be more applicable to regular drinkers and borderline-alcoholics (our mice don’t drink and crave enough alcohol to be considered full-blown alcoholics). These data are relevant to a unique drinking population because our mice received extremely large doses of alcohol (enough to cause them to “pass out” for a few hours [i.e. shotgunning beers]) over a short period of time.
The first experimental aim characterized the extent and time course of peak alcohol concentrations detected in the circadian clock. As shown here, peak concentrations are dose-dependent, but the time at which these peak concentrations are reached is within a 20-40 min time window.
Given that there is a 20-40 min time window in which alcohol levels are maximal in the circadian clock, we paired this physiological event with a phase-delaying light pulse or phase-advancing serotonergic injection. As shown, acute alcohol dose-dependently attenuated adaptation (entrainment) to a light pulse, but only had an effect on adaptation to (nonphotic) serotonin stimuli at the highest dose.
The most mechanistically revealing study in this paper was the fact that a direct perfusion of alcohol into the SCN at a dose comparable to the highest dose administered (i.p.) in the prior studies caused impairment of photic entrainment to a comparable extent. In lieu of this impairment, alcohol, administered alone, had no effect on basal circadian clock neuronal activity (characterized through FOS expression) as found also found in vitro.
Though the data were not presented in this paper, but can be found in my dissertation, an acute SCN alcohol perfusion did not affect nonphotic entrainment. This suggests that alcohol-induced impairments of the two main types of circadian entrainment (photic and nonphotic) are regulated by separate brain areas/systems. It’s likely that alcohol disruption to nonphotic entrainment processess occurs at the level of the raphe nuclei (midbrain) and/or intergeniculate leaflet (thalamus) which transmit such information to the circadian clock.
From a experimental perspective, this study lends credence to a series of in vivo and in vitro studies showing the direct, deleterious effects of alcohol on circadian clock function that have been published over the past few years. More importantly, it presents a mechanism through which alcohol disrupts timed physiology and behavior, that could, if perturbed often, could lead to alcohol dependence.
Brager AJ, Ruby CL, Prosser RA, & Glass JD (2011). Acute ethanol disrupts photic and serotonergic circadian clock phase-resetting in the mouse. Alcoholism, clinical and experimental research, 35 (8), 1467-74 PMID: 21463340