Developmental Alcohol Exposure Alters Light‐Induced Phase Shifts of the Circadian Activity Rhythm in Rats

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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.