Developmental alcohol exposure alters light-induced phase shifts of the circadian activity rhythm in rats.
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.
Farnell
Yuhua Z
YZ
Department of Human Anatomy and Medical Neurobiology, Texas A&M University System Health Science Center, College of Medicine, College Station, Texas 77843-1114, USA.
West
James R
JR
Chen
Wei-Jung A
WJ
Allen
Gregg C
GC
Earnest
David J
DJ
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000254:growth & development*
D000431:Ethanol