Abstract
Prenatal alcohol exposure can produce long-lasting cognitive and learning impairments in children. Previous studies have suggested that prenatal ethanol exposure can produce neurochemical abnormalities in hippocampal formation. We examined whether performance in the Morris water task, known to be sensitive to interference with hippocampal function, would be affected in adult offspring of rat dams who consumed moderate levels of ethanol through pregnancy. Rat dams consumed one of three diets throughout gestation: (1) Bio-Serve liquid diet containing 5% ethanol (v/v; 26% EDC), which produces a maternal peak blood ethanol concentration of 100 mg/dl; (2) pair fed an isocalorically equivalent amount of 0% ethanol liquid diet; or (3) laboratory chow ad libitum. Adult offspring from each of the three maternal diet conditions were trained in one of three versions of the Morris water task. We employed the “standard” fixed hidden platform task, the moving platform task, and a task that measures competition between cue and place navigation. All three groups learned to navigate normally in the fixed hidden platform version and showed clear preferences for the goal location during no-platform probe trials. In contrast, in the moving platform version and the cue versus place competition task, the prenatally exposed rats were abnormal relative to the rats of the other two maternal diet conditions. In both of these tasks, they behaved in a manner consistent with the idea that acquisition of new place information does not proceed as effectively as in normal rats. These data are consistent with the hypothesis that hippocampal circuitry and neurochemistry related to synaptic plasticity are important targets underlying at least some of the long-lasting deleterious cognitive effects of prenatal alcohol exposure.
Article PDF
Similar content being viewed by others
References
Abel, E. L. (1984). Prenatal effects of ethanol. Drug & Alcohol Dependence, 14, 1–10.
Allan, A. M., Caldwell, K. K., & Savage, D. D. (1997). Effects of prenatal ethanol exposure on phospholipase C and A2 in rat hippocampus and medial frontal cortex. Alcoholism: Clinical & Experimental Research, 21, 1534–1541.
Allan, A. M., Wu, H., Paxton, L. L., & Savage, D. D. (1998). Prenatal ethanol exposure alters the modulation of the gamma-aminobutyric acid A1 receptor-gated chlorideion channel in adult rat offspring. Journal of Pharmacology & Experimental Therapeutics, 284, 250–257.
Auer, R. N., Jensen, M. L., & Whishaw, I. Q. (1989). Neurobehavioral deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus. Journal of Neuroscience, 9, 1641–1647.
Berman, R. E., & Hannigan, J. H. (2000). Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy. Hippocampus, 10, 94–110.
Blanchard, B. A., Pilati, M. L., & Hannigan, J. H. (1990). The role of stress and age in spatial navigation deficits following prenatal exposure to ethanol. Psychobiology, 18, 48–54.
Blanchard, B. A., Riley, E., & Hannigan, J. H. (1987). Deficits on a spatial navigation task following prenatal exposure to ethanol. Neurotoxicology & Teratology, 9, 253–258.
Castro, C. A., Silbert, L. H., McNaughton, B. L., & Barnes, C. A. (1989). Recovery of spatial learning deficits after decay of electrically induced synaptic enhancement in the hippocampus. Nature, 342, 545–548.
Centers for Disease Control and Prevention. (1994). Frequent alcohol consumption among women of childbearing age-Behavioral risk factor surveillance system, 1991. Journal of the American Medical Association., 271, 1820–1821.
Clarren, S. K., & Smith, D. W. (1978). The fetal alcohol syndrome. New England Journal of Medicine, 298, 1063–1067.
Conry, J. (1990). Neuropsychological deficits in fetal alcohol syndrome and fetal alcohol effects. Alcoholism: Clinical & Experimental Research, 14, 650–661.
Farr, K. L., Montano, C. Y., Paxton, L. L., & Savage, D. D. (1988). Prenatal ethanol exposure decreases hippocampal 3H-vinylidene kainic acid binding in 45-day-old rats. Neurotoxicology & Teratology, 10, 563–568.
Gianoulakis, C. (1990). Rats exposed prenatally to alcohol exhibit impairment in spatial navigation test. Behavioural Brain Research, 36, 217–228.
Hanson, J. W., Streissguth, A. P., & Smith, D. W. (1978). The effects of moderate alcohol consumption during pregnancy on fetal growth and morphogenesis. Journal of Pediatrics, 92, 457–460.
Jacobson, J. L., Jacobson, S. W., & Sokol, R. J. (1994). Effects of fetal alcohol exposure on infant reaction-time. Alcoholism: Clinical & Experimental Research, 18, 1125–1132.
Jacobson, J. L., Jacobson, S. W., Sokol, R. J., Martier, S. S., Ager, J. W., & Kaplan-Estrin, M. G. (1993). Teratogenic effects of alcohol on infant development. Alcoholism: Clinical & Experimental Research, 17, 174–183.
Jones, K. L., & Smith, D. W. (1973). Recognition of the fetal alcohol syndrome in early infancy. Lancet, 2, 99–101.
Jones, K. L., Smith, D. W., Ulleland, C. N., & Streissguth, A. P. (1973). Patterns of malformation in offspring of chronic alcoholic mothers. Lancet, 1, 1267–1271.
Kelly, S., Goodlett, C. R., Hulsether, S., & West, J. (1988). Impaired spatial navigation in adult female but not adult male rats exposed to alcohol during the brain growth spurt. Behavioural Brain Research, 27, 247–257.
Kim, C. K., Kalynchuk, L. E., Kornecook, T. J., Redil, V. A., McIntyre, C. P., Mumby, D. G., Pinel, J. P. J., & Weinberg, J. (1992). Prenatal ethanol exposure and nonspatial versus spatial learning/memory in rats. Society for Neuroscience Abstracts, 23, 1237.
Lemoine, P., Haronsseau, H., Borteryu, J. P., & Menuet, J. C. (1968). Les enfants des parents alcooliques: Anomalies observées à propos de 127 cas [Children of alcoholic parents: Abnormalities observed on the basis of 127 cases]. Ouest Medecine, 25, 476–482.
Mattson, S. N., Riley, E. P., Gramling, L., Delis, D. C., & Jones, K. L. (1997). Heavy prenatal alcohol exposure with or without physical features of fetal alcohol syndrome leads to IQ deficits. Journal of Pediatrics, 131, 718–721.
McDonald, R. J., & White, N. M. (1994). Parallel information-processing in the water maze: Evidence for independent memory systerns involving dorsal striatum and hippocampus. Behavioral & Neural Biology, 61, 260–270.
Milner, B. (1965). Visually-guided maze learning in man: Effects of bilateral hippocampal, bilateral frontal, and unilateral cerebral lesions. Neuropsychologia, 6, 215–234.
Morris, R. G. M. (1981). Spatial localization does not require the presence of local cues. Learning & Motivation, 12, 239–261.
Morris, R. G. M., Anderson, E., Lynch, G. S., & Baudry, M. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature, 319, 774–776.
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O’Keefe, J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature, 297, 681–683.
Perrone-Bizzozero, N. I., Isaacson, T. V., Keidan, G., Eriqat, C., Meiri, K. F., Savage, D. D., & Allan, A. M. (1998). Prenatal exposure decreases GAP-43 phosphorylation and protein kinase C activity in the hippocampus of adult rat offspring. Journal of Neurochemistry, 71, 2104–2111.
Queen, S. A., Sanchez, C. F., Lopez, S. R., Paxton, L. L., & Savage, D. D. (1993). Dose and age dependent effects of prenatal ethanol exposure on hippocampal metabotropic-glutamate receptor-stimulated phosphoinositide hydrolysis. Alcoholism: Clinical & Experimental Research, 17, 887–893.
Savage, D. D., Cruz, L. L., Duran, L. M., & Paxton, L. L. (1998). Prenatal ethanol exposure diminishes activity-dependent potentiation of amino acid transmitter release in adult rat offspring. Journal of Pharmacology & Experimental Therapeutics, 284, 250–257.
Savage, D. D., Montano, C. Y., Otero, M. A., & Paxton, L. L. (1991). Prenatal ethanol exposure decreases hippocampal NMDA-sensitive [3H]-glutamate binding site density in 45-day-old rat. Alcohol, 8, 193–201.
Shaywitz, S. F., Cohen, D. J. & Shaywitz, B. A. (1980). Behavior and learning difficulties in children of normal intelligence born to alcoholic mothers. Journal of Pediatrics, 96, 978–982.
Skelton, R. W., & McNamara, R. K. (1992). Bilateral knife cuts to the perforant path disrupt spatial learning in the Morris water maze. Hippocampus, 2, 73–80.
Squire, L. (1992). Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychological Review, 99, 195–231.
Streissguth, A. P., Aase, J. M., Clarren, S. K., Randels, S. P., LaDue, R. A., & Smith, D. F. (1991). Fetal alcohol syndrome in adolescents and adults. Journal of the American Medical Association, 265, 1961–1967.
Streissguth, A., Barr, H., & Sampson, P. (1990). Moderate prenatal alcohol exposure: Effects on child I.Q. and learning problems at age 7½ years. Alcoholism: Clinical & Experimental Research, 14, 662–669.
Sutherland, R. J., Dringenberg, H. C., & Hoesing, J. M. (1993). Induction of long-term potentiation at perforant path dentate synapses does not affect place learning or memory. Hippocampus, 3, 141–147.
Sutherland, R. J., Hoesing, J. M., & Whishaw, I. Q. (1990). Domoic acid, an environmental toxin, produces hippocampal damage and severe memory impairment. Neuroscience Letters, 120, 221–223.
Sutherland, R. J., Kolb, B., & Whishaw, I. Q. (1982). Spatial mapping: Definitive disruption by hippocampal and frontal cortex damage in the rat. Neuroscience Letters, 31, 271–276.
Sutherland, R. J., McDonald, R. J., & Savage, D. D. (1997). Prenatal exposure to moderate levels of ethanol can have long-lasting effects on hippocampal synaptic plasticity in adult offspring. Hippocampus, 7, 232–238.
Sutherland, R. J., & Rodriguez, A. J. (1989). On the role of the fornix and related subcortical structures in spatial learning and memory. Behavioural Brain Research, 32, 265–277.
Sutherland, R. J., Whishaw, I. Q., & Kolb, B. (1983). A behavioural analysis of spatial localization following electrolytic, kainate-, or colchicine-induced damage to the hippocampal formation in the rat. Behavioural Brain Research, 7, 133–153.
Whishaw, I. Q. (1985). Formation of place learning-set by the rat: A new paradigm for neurobehavioral studies. Physiology & Behavior, 35, 139–143.
Whishaw, I. Q. (1987). Hippocampal, granule cell and CA3-4 lesions impair formation of a place learning-set in the rat and induce reflex epilepsy. Behavioural Brain Research, 24, 59–72.
Zola-Morgan, S., Squire, L., & Amaral, D. (1986). Human amnesia and the medial temporal lobe region: Enduring memory impairment after a bilateral lesion limited to CA1 field of the hippocampus. Journal of Neuroscience, 6, 2950–2967.
Author information
Authors and Affiliations
Corresponding author
Additional information
This research was supported by a grant from the NSERC of Canada (to R.J.S. & R.J.M.), NIH Grants AA11333 and AA06548 (to R.J.S. and D.D.S., respectively), Grant RR08139 from the Minority Biomedical Research Support Program (to D.D.S.), and a grant from the Dedicated Health Research Fund of the University of New Mexico School of Medicine (to D.D.S.). The authors thank Linda Paxton, Christian Sanchez, Samantha Lopez, Ana Polaco, Laura Cruz, Jeremy Hanlon, and Lorina Duran for their work on the fetal ethanol exposure paradigm. The au-thors also thank Lisa Mumby and Brenton Cooper for their participation in the behavioral testing.
Rights and permissions
About this article
Cite this article
Sutherland, R.J., McDonald, R.J. & Savage, D.D. Prenatal exposure to moderate levels of ethanol can have long-lasting effects on learning and memory in adult offspring. Psychobiology 28, 532–539 (2000). https://doi.org/10.3758/BF03332012
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.3758/BF03332012