Choline supplementation attenuates learning deficits associated with neonatal alcohol exposure in the rat: effects of varying the timing of choline administration.
Despite the harmful effects of fetal alcohol exposure, some pregnant women continue to drink alcohol. Thus, it is imperative to pursue safe, effective treatments for children with fetal alcohol spectrum disorders. Using an animal model, our laboratory has demonstrated that choline, an essential nutrient, effectively reduces the severity of some fetal alcohol effects, even when administered after the ethanol insult is complete. The present study investigated whether there is a critical developmental period when choline is most effective in attenuating ethanol's teratogenic effects. Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol during the third trimester equivalent brain growth spurt (postnatal days (PD) 4-9) via intubation. A non-intubation control group and a sham intubation control group were included. Following ethanol exposure, pups received subcutaneous injections of saline vehicle or choline chloride (100 mg/kg/day) from PD 11-20, PD 21-30, or PD 11-30. Beginning on PD 45, subjects were tested on a Morris water maze spatial learning task. Performance of both the ethanol-exposed group that did not receive choline and the ethanol-exposed group treated with choline from PD 21-30 was significantly impaired compared to controls during acquisition of the Morris water maze task. Performance of ethanol-exposed groups treated with choline from PD 11-20 or PD 11-30 was intermediate, not differing significantly from any other groups. However, during the probe trial, ethanol exposure produced significant deficits in spatial memory which were mitigated by all choline treatments, regardless of the timing of administration. These findings suggest that choline's therapeutic window may be very large, or spans across the two developmental periods examined in this study. Importantly, these findings indicate that choline supplementation may effectively reduce some alcohol-related learning impairments, even when administered in later childhood.
Ryan
S Hunter
SH
Department of Psychology, Center for Behavioral Teratology, San Diego State University, San Diego, CA 92120, USA.
Williams
Jennifer K
JK
Thomas
Jennifer D
JD
D000367:Age Factors; D000438:Alcohols / Q000009:adverse effects* / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002794:Choline / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D007859:Learning Disabilities / Q000097:blood / Q000178:diet therapy* / Q000209:etiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018697:Nootropic Agents / Q000008:administration & dosage*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012737:Sex Factors; D013997:Time Factors
D000438:Alcohols; D018697:Nootropic Agents; D002794:Choline
Alcohol Clin Exp Res. 1997 Feb;21(1):150-61
9046388
Behav Brain Res. 1988 Mar;27(3):247-57
3358862
Neurotoxicol Teratol. 2004 Jan-Feb;26(1):35-45
15001212
Neurotoxicol Teratol. 1997 Nov-Dec;19(6):435-46
9392779
Teratology. 1997 Nov;56(5):317-26
9451756
Nutr Rev. 2006 Apr;64(4):197-203
16673755
Alcohol Clin Exp Res. 1999 Jun;23(6):1070-6
10397293
Annu Rev Nutr. 1994;14:269-96
7946521
Behav Neurosci. 2007 Feb;121(1):120-30
17324056
Neurotoxicol Teratol. 2000 Jan-Feb;22(1):103-11
10642119
Epilepsy Res. 2002 Jan;48(1-2):3-13
11823105
Behav Brain Res. 1999 Nov 15;105(2):173-88
10563491
Alcohol Clin Exp Res. 1996 Sep;20(6):1088-93
8892532
Neurosci Biobehav Rev. 2006;30(5):696-712
16504295
Dev Biol. 1974 Jan;36(1):130-41
4822829
J Neurophysiol. 2004 Apr;91(4):1545-55
14645379
Annu Rev Nutr. 2006;26:229-50
16848706
Hippocampus. 2000;10(1):94-110
10706221
Neurology. 2001 Jul 24;57(2):235-44
11468307
Neurotoxicol Teratol. 1993 Jul-Aug;15(4):261-6
8413080
J Pharmacol Exp Ther. 1992 Sep;262(3):1128-32
1326624
Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1028-34
16157106
Behav Neurosci. 2006 Apr;120(2):482-7
16719711
Adv Exp Med Biol. 1991;295:373-82
1776578
Neurotoxicol Teratol. 2000 Jan-Feb;22(1):125-32
10642121
Alcohol Res Health. 2001;25(3):185-91
11810956
Dev Neurosci. 2005 Jan-Feb;27(1):13-9
15886480
Front Integr Neurosci. 2008 May 03;1:7
18958235
Brain Res. 2002 May 24;937(1-2):83-93
12020866
Behav Neurosci. 2008 Dec;122(6):1264-73
19045946
FASEB J. 2006 Jan;20(1):43-9
16394266
Behav Neurosci. 1989 Dec;103(6):1234-41
2610916
Dev Neurosci. 1999;21(2):94-104
10449981
Alcohol Clin Exp Res. 2007 Aug;31(8):1425-34
17550365
Neuron. 2005 Apr 21;46(2):173-9
15848797
Early Hum Dev. 1979 Mar;3(1):79-83
118862
J Consult Clin Psychol. 2006 Aug;74(4):639-48
16881771
Cereb Cortex. 2008 Jan;18(1):136-44
17443018
JAMA. 2003 Dec 10;290(22):2996-9
14665662
Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8543-8
12808140
Alcohol Clin Exp Res. 1996 Feb;20(1):31-4
8651458
Eur J Neurosci. 2005 Mar;21(6):1719-26
15845099
Neurotoxicol Teratol. 2000 Mar-Apr;22(2):143-9
10758343
Brain Res Dev Brain Res. 2000 Sep 30;123(1):25-32
11020547
Exp Biol Med (Maywood). 2005 Jun;230(6):357-65
15956765
Alcohol Clin Exp Res. 2001 May;25(5):764-73
11371726
Dev Med Child Neurol. 2002 Feb;44(2):98-106
11848116
J Biol Chem. 2007 Oct 26;282(43):31777-88
17724018
Alcohol Clin Exp Res. 2001 May;25(5 Suppl ISBRA):202S-206S
11391072
Alcohol Clin Exp Res. 2007 May;31(5):868-79
17386071
Brain Res. 1998 Jun 1;794(2):225-38
9622639
Dev Biol. 1974 Jan;36(1):142-54
4822830
J Neurochem. 2004 Jun;89(6):1368-77
15189339
J Neurophysiol. 1998 Apr;79(4):1790-6
9535948
Neuroreport. 2005 Aug 22;16(12):1285-90
16056126
Brain Res Dev Brain Res. 2003 Jan 10;140(1):15-28
12524173
Neurotoxicol Teratol. 2000 Sep-Oct;22(5):703-11
11106863
J Pharmacol Exp Ther. 2002 Oct;303(1):110-6
12235240
FASEB J. 1998 Mar;12(3):349-57
9506479
J Neurosci. 2008 Feb 6;28(6):1313-9
18256251
Dev Med Child Neurol. 1999 Oct;41(10):652-9
10587040
PLoS Med. 2006 Apr;3(4):e101
16478293
Alcohol Clin Exp Res. 1995 Oct;19(5):1198-202
8561290
J Comp Neurol. 2005 May 23;486(1):61-75
15834959
J Physiol Paris. 1998 Jun-Aug;92(3-4):199-203
9789808
Neuroreport. 1997 Sep 29;8(14):3053-9
9331913
Dev Psychobiol. 1988 May;21(4):339-53
3378679
Brain Res Dev Brain Res. 1999 Dec 10;118(1-2):159-67
10611515
Neurosci Biobehav Rev. 2007;31(2):239-45
17097730
J Pediatr. 2006 Nov;149(5 Suppl):S131-6
17212955
Neurosci Biobehav Rev. 2003 Sep;27(4):385-99
12946691