Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats.
In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid brain growth produces structural damage in some brain regions that often persists into adulthood and thus may have long-term consequences in the neural regulation of behavior. Because recent findings indicate that the circadian clock located in the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during development, the present study examined the long-term effects of neonatal alcohol exposure on the photic regulation of circadian behavior in adult rats. Rat pups were exposed to alcohol (3.0, 4.5, or 6.0 g x kg(-1) x day(-1)) or isocaloric milk formula on postnatal days 4-9 using artificial-rearing methods. At 2 months of age, animals were housed individually and circadian wheel-running behavior was continuously analyzed to determine the effects of neonatal alcohol treatment on the rate of reentrainment to a 6-h advance in the 12-h light:12-h dark photoperiod and the phase-shifting properties of free-running rhythms in response to discrete light pulses on a background of constant darkness. For all doses, neonatal alcohol exposure had a significant effect in reducing the time for reentrainment such that EtOH-treated rats required four to five fewer days than control animals for stable realignment of the activity rhythm to the shifted light-dark cycle. Coupled with the accelerated rate of reentrainment, the amplitude of light-evoked phase delays at circadian time 14 and advances at circadian time 22 in the 4.5 and 6.0 g x kg(-1) x day(-1) EtOH groups was almost twofold greater than that observed in control animals. The present observations indicate that the mechanisms by which photic signals regulate circadian behavior are permanently altered following alcohol exposure during the period of rapid brain development. These long-term alterations in the photic regulation of circadian rhythms may account, at least partially, for some neurobehavioral consequences of prenatal alcohol exposure in humans such as depression.
Allen
Gregg C
GC
Department of Human Anatomy and Medical Neurobiology, The Texas A&M University System Health Science Center, College of Medicine, 228 Reynolds Medical Building, College Station, TX 77843-1114, USA.
Farnell
Yuhua Z
YZ
Maeng
Ji-ung
JU
West
James R
JR
Chen
Wei-Jung A
WJ
Earnest
David J
DJ
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D002940:Circadian Rhythm / Q000502:physiology*; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D008027:Light; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D000431:Ethanol