Chronic Ethanol Intake Alters Circadian Period‐Responses to Brief Light Pulses in Rats

Abstract

Although chronic alcohol intake is associated with widespread disruptions of sleep-wake cycles and other daily biological rhythms in both human alcoholics and experimental animals, the extent to which the chronobiological effects of alcohol are mediated by effects on the underlying circadian pacemaker remains unknown. Nevertheless, recent studies indicate that both adult and perinatal ethanol treatments may alter the free-running period and photic responsiveness of the circadian pacemaker. The present experiment was designed to further characterize the effects of chronic ethanol intake on the response of the rat circadian pacemaker to brief light pulses. Ethanol-treated and control animals were exposed to 15-min light pulses during either early or late subjective night on the first day of constant darkness following entrainment to a 12:12 light-dark cycle. Relative to pulses delivered during early subjective night and to "no-pulse" conditions, light pulses delivered during late subjective night resulted in period-shortening after-effects under constant darkness, but only in control animals, not in ethanol-treated animals. These results indicate that chronic ethanol intake reduces the responsiveness of the circadian pacemaker to acute photic stimulation, and suggest that the chronobiological disruptions seen in human alcoholics are due in part to alterations in circadian pacemaker function.

Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster

“…These results confirm and extend our previous work on the chronobiological effects of ethanol intake in rats (Dwyer and Rosenwasser, 1998;Fecteau et al, 2006;Rosenwasser et al, 2005aRosenwasser et al, ,2005b, and provide additional evidence that ethanol alters fundamental properties of the underlying circadian pacemaker.…”

“…In addition, photic signaling in SCN neurons is modulated by GABAergic mechanisms, and both GABA-A and GABA-B agonists generally inhibit the circadian phase-shifting effects of light (Gillespie et al, 1997;Mintz et al, 2002;Menaker, 1986,1989). Despite discrepant findings in the literature regarding direct GABA-A agonists that may be related to central vs. peripheral sites of administration (Gillespie et al, 1997;Ralph and Menaker, 1989), peripheral administration of indirect GABA-A agonists (i.e., benzodiazepines) selectively blocks the phase-advancing but not the phase-delaying effects of light (Ralph and Menaker, 1986), similar to the effects of chronic ethanol intake seen here and in our previous study using rats (Rosenwasser et al, 2005b). On the other hand, since chronic ethanol treatment is known to up-regulate NMDA receptors (Faingold et al, 1998), one might have predicted that this treatment would actually potentiate light-induced phase responses, in contrast to the observed phase-specific blocking of photic phase responses.…”

“…In addition, chronic ethanol intake attenuates the period-altering aftereffects of brief light pulses presented during late subjective night (but not early subjective night) (Rosenwasser et al, 2005b). While the period and phase of the circadian pacemaker may be influenced by both spontaneous and evoked activity (Mistlberger et al, 1998;Mrosovsky, 1996bMrosovsky, ,1999Van Reeth and Turek, 1989), changes in daily wheel running during ethanol intake in these studies were modest and did not appear to be correlated with effects on free-running rhythms (Mistlberger and Nadeau, 1992;Rosenwasser et al, 2005a).…”

“…The response to light pulses was examined because light pulses are the most widely studied circadian phaseshifting stimulus, and because of our earlier finding that chronic ethanol intake modifies the period altering effects of light pulses in rats (Rosenwasser et al, 2005b). The response to triazolam injections was examined because triazolam and other benzodiazepines produce large amplitude circadian phase responses thought to be mediated by benzodiazepine binding to GABA-A receptors in the SCN and other neural components of the circadian system (Smith and Turek, 1989;Turek and Losee-Olson, 1986).…”

Evening Alcohol Suppresses Salivary Melatonin in Young Adults

“…For example, Rosenwasser et al (2005) assessed the effects of chronic ethanol on the response of the circadian pacemaker to brief light pulses in rats and found that control animals displayed a marked period-shortening aftereffect in comparison to ethanol treated animals following a light pulse, thus suggesting that the chronobiological effects of ethanol are due in part to alterations at the level of the underlying circadian pacemaker.…”