Developmental alcohol exposure alters light-induced phase shifts of the circadian activity rhythm in rats

Abstract

Background: Developmental alcohol (EtOH) exposure produces long-term changes in the photic regulation of rat circadian behavior. Because entrainment of circadian rhythms to 24-hr light/dark cycles is mediated by phase shifting or resetting the clock mechanism, we examined whether developmental EtOH exposure also alters the phase-shifting effects of light pulses on the rat activity rhythm.

Methods: Artificially reared Sprague-Dawley rat pups were exposed to EtOH (4.5 g/kg/day) or an isocaloric milk formula (gastrostomy control; GC) on postnatal days 4 to 9. At 2 months of age, rats from the EtOH, GC, and suckle control groups were housed individually, and wheel-running behavior was continuously recorded first in a 12-hr light/12-hr dark photoperiod for 10 to 14 days and thereafter in constant darkness (DD). Once the activity rhythm was observed to stably free-run in DD for at least 14 days, animals were exposed to a 15-min light pulse at either 2 or 10 hr after the onset of activity [i.e., circadian time (CT) 14 or 22, respectively], because light exposure at these times induces maximal phase delays or advances of the rat activity rhythm.

Results: EtOH-treated rats were distinguished by robust increases in their phase-shifting responses to light. In the suckle control and GC groups, light pulses shifted the activity rhythm as expected, inducing phase delays of approximately 2 hr at CT 14 and advances of similar amplitude at CT 22. In contrast, the same light stimulus produced phase delays at CT 14 and advances at CT 22 of longer than 3 hr in EtOH-treated rats. The mean phase delay at CT 14 and advance at CT 22 in EtOH rats were significantly greater (p < 0.05) than the light-induced shifts observed in control animals.

Conclusions: The data indicate that developmental EtOH exposure alters the phase-shifting responses of the rat activity rhythm to light. This finding, coupled with changes in the circadian period and light/dark entrainment observed in EtOH-treated rats, suggests that developmental EtOH exposure may permanently alter the clock mechanism in the suprachiasmatic nucleus and its regulation of circadian behavior.

Fig. 1

Effects of developmental alcohol exposure on light-induced phase shifts of the rat activity rhythm: representative activity records of three adult male rats from the SC, GC, and EtOH groups that were maintained in DD and exposed to a 15-min light pulse at CT 14 (A) or CT 22 (B). Actograms are double-plotted over 48 hr, and shaded circles (with a starred inset) on each record indicate the day and time during which animals were exposed to the light pulse (LP). A line has been fitted through the activity onsets for 7 to 13 days before the light pulse and extended for 25 days after treatment to facilitate visualization of phase shifts in free-running activity rhythm. In EtOH rats, exposure to a 15-min light pulse induced phase delays of the activity rhythm at CT 14 and advances at CT 22 that were larger than those observed in the SC and GC animals.

Fig. 2

Effects of developmental alcohol exposure on the phase-shifting responses of the rat activity rhythm to light at CT 14 and 22. The mean ± SEM phase shift (ΔΦ) is shown (in hours) of the activity rhythm induced by a 15-min light pulse at CT 14 or 22 in SC, GC, and EtOH rats. Phase delays are indicated by negative values, and advances are denoted by positive values. Light-induced phase delays at CT 14 and phase advances at CT 22 in EtOH rats were significantly greater (*p < 0.05) than those observed in the SC and GC groups.