Prenatal Ethanol (EtOH) Exposure Alters the Sensitivity of the Adult Dentate Gyrus to Acute EtOH Exposure

Authors

  • Jennifer L. Helfer,

    1. Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
    2. Department of Biology, University of Victoria, Victoria, Canada
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  • Emily R. White,

    1. Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
    2. Graduate Program in Neuroscience, University of Victoria, Victoria, BC, Canada
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  • Brian R. Christie

    Corresponding author
    1. Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
    2. Department of Biology, University of Victoria, Victoria, Canada
    3. Graduate Program in Neuroscience, University of Victoria, Victoria, BC, Canada
    4. Graduate Program in Neuroscience and the Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
    5. The Brain Research Centre, University of British Columbia, Vancouver, BC, Canada
    • Reprint requests: Brian R. Christie, PhD, Division of Medical Sciences, University of Victoria, 3800 Finnerty Road, Victoria, BC V8P 5C2, Canada; Tel.: 250-472-4244; Fax: 250-472-5505; E-mail: brain64@uvic.ca

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Abstract

Background

Prenatal ethanol (EtOH) exposure results in a spectrum of structural, cognitive, and behavioral abnormalities, collectively termed “fetal alcohol spectrum disorders” (FASDs). The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of EtOH. Prenatal EtOH exposure can lead to long-lasting impairments in the ability to process spatial information, as well as produce long-lasting deficits in the ability of animals to exhibit long-term potentiation (LTP), a biological model of learning and memory processing. These deficits also have the ability to facilitate EtOH and/or other drug abuse later in life. This study sought to determine prenatal EtOH exposure altered the effects of acute EtOH application on synaptic plasticity.

Methods

Prenatal EtOH exposure was modeled using a liquid diet where dams were given 1 of 3 diets: (i) a liquid diet containing EtOH (35.5% EtOH-derived calories), (ii) a liquid diet, isocaloric to the EtOH diet, but with maltose–dextrin substituting for the EtOH-derived calories, and (iii) an ad libitum diet of standard rat chow. Extracellular recordings from transverse brain slices (350 μm) prepared from 50- to 70-day-old rats, following prenatal EtOH exposure (gestational day 1 to 21). LTP was examined in the dentate gyrus following acute EtOH exposure (0, 20, or 50 mM) in these slices.

Results

Prenatal EtOH exposure attenuated LTP in the adult dentate gyrus. In control offspring, acute application of EtOH in adulthood attenuated (20 mM) or blocked (50 mM) LTP. Conversely, the effect of acute EtOH application on LTP was not as pronounced in prenatal EtOH offspring.

Conclusions

Prenatal EtOH exposure alters the sensitivity of the adult dentate gyrus to acute EtOH application producing a long-lasting tolerance to the inhibitory effects of EtOH. This decreased sensitivity may provide a mechanism promoting the formation of drug-associated memories and help explain the increased likelihood of developing an alcohol dependency often observed in individuals with FASDs.

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