Elsevier

Alcohol

Volume 19, Issue 2, October 1999, Pages 107-111
Alcohol

Articles
Age and Dose-Dependent Effects of Ethanol on the Induction of Hippocampal Long-Term Potentiation

https://doi.org/10.1016/S0741-8329(99)00021-XGet rights and content

Abstract

Hippocampal long-term potentiation (LTP) is strongly associated with the acquisition of spatial memory and is attenuated by ethanol. Recent studies have shown that the inhibitory potency of ethanol against n-methyl-d-aspartate (NMDA) receptor-mediated synaptic activity is enhanced in hippocampal slices taken from juvenile rats compared to those taken from adults. In addition, ethanol has been reported to impair spatial memory acquisition at lower doses in adolescent rats compared to adults. We therefore hypothesized that the suppression of hippocampal LTP by ethanol would be more potent in hippocampal slices taken from adolescent rats compared to those taken from adults. The potency of ethanol against NMDA receptor-mediated LTP was assessed in area CA1 of hippocampal slices taken from adolescent (30 days old) and adult (90 days old) rats. In slices from adolescent rats, theta-burst stimulus trains reliably induced robust LTP in the absence of ethanol, but when the stimulus trains were presented in the presence of either 10 mM or 30 mM ethanol, LTP induction was significantly suppressed relative to controls. In contrast, there was no effect of these ethanol concentrations on the induction of LTP in hippocampal slices from adult rats. These observations indicate that ethanol suppresses LTP in the adolescent hippocampus at concentrations that do not affect than it suppresses in the adult slices, suggesting a much greater sensitivity to ethanol in adolescence.

Section snippets

Hippocampal Slice Preparation

Male Sprague-Dawley rats, 30 days old (adolescent, n = 22) and 90 days old (adult, n = 16), were used as subjects. The animals were sacrificed with an overdose of Halothane, and the brain was quickly removed and placed in ice-cold, oxygenated artificial cerebrospinal fluid (ACSF), which contained (in mM) NaCl, 124; KCl, 3.25; NaH2PO4, 1.25; NaHCO3, 25; CaCl2, 2.4; MgSO4, 2.0; and dextrose, 10. The ACSF was oxygenated with 95% O2: 5% CO2 to maintain pH = 7.4. The hippocampi were dissected from

Results

Under control conditions, robust LTP was induced in hippocampal slices from both adolescent (242 ± 24% of baseline pEPSP slope) and adult (191 ± 23%) rats. Although there was a clear trend toward greater LTP magnitude among the slices from adolescent animals, this trend did not reach statistical significance [F(1, 71) = 3.27, p = 0.075].

There was no significant effect of ethanol on the slope of the baseline pEPSPs during the 30-min ethanol exposure period. However, the presence of ethanol

Discussion

The principal finding of this study is that ethanol attenuated the induction of LTP in hippocampal slices from adolescent rats at physiological concentrations that were ineffective in slices from adults. Both 10 mM and 30 mM ethanol significantly depressed the induction of LTP in slices from adolescent rats, but neither of these concentrations attenuated the induction of LTP in slices from adults. This finding is consistent with our previous report that ethanol attenuates NMDA receptor-mediated

Acknowledgements

This work was funded in part by National Institutes of Health Grants AG13165 to DAT and AA11088 to HSS, by a VA Merit Review Award to DAT, and by VA Research Career Scientist Awards to HSS and WAW.

References (26)

  • P Little et al.

    Differential effects of ethanol in adolescent and adult rats

    Alcohol. Clin. Exp. Res.

    (1996)
  • D Lovinger et al.

    NMDA receptor mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from the adult rat

    J. Neurosci.

    (1990)
  • B Markwiese et al.

    Differential effects of ethanol on memory in adolescent and adult rats

    Alcohol. Clin. Exp. Res.

    (1998)
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