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Aniracetam Reversed Learning and Memory Deficits Following Prenatal Ethanol Exposure by Modulating Functions of Synaptic AMPA Receptors

Neuropsychopharmacology volume 33, pages 10711083 (2008) | Download Citation

Abstract

Specific pharmacological treatments are currently not available to address problems resulting from fetal ethanol exposure, described as Fetal Alcohol Syndrome or Fetal Alcohol Spectrum Disorders (FASD). The present study evaluated the therapeutic effects of aniracetam against cognitive deficits in a well-characterized and sensitive FASD Sprague–Dawley rat model. Ethanol, administered orally at a moderate dose (4 g/kg/24 h; 38% v/v) during the entire course of pregnancy, caused severe cognitive deficits in offspring. Furthermore, both progeny genders were affected by a spectrum of behavioral abnormalities, such as a delay in the development of the righting reflex, poor novelty seeking behavior, and high anxiety levels in female rats. Cognitive disabilities, monitored in adult rats by a two-way active avoidance task, correlated well with a significant reduction of AMPA (α-amino-3 hydro-5 methyl-isoxazole propionic acid) receptor-mediated miniature excitatory postsynaptic responses (mEPSCs) in the hippocampus. Administration of aniracetam for 10 days (post-natal days (PND) 18–27), at a dose of 50 mg/kg reversed cognitive deficits in both rat genders, indicated by a significant increase in the number of avoidances and the number of ‘good learners’. After the termination of the nootropic treatment, a significant increase in both amplitude and frequency of AMPA receptor-mediated mEPSCs in hippocampal CA-1 pyramidal cells was observed. Significant anxiolytic effects on PND 40 also preceded acquisition improvements in the avoidance task. This study provides evidence for the therapeutic potential of aniracetam in reversing cognitive deficits associated with FASD through positive post-natal modulation of AMPA receptors.

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Acknowledgements

We gratefully acknowledge Dr Norou Diawara at Old Dominion University, VA, for the electrophysiology statistical analysis discussion. We are grateful to Gerritt Dewitt from Digital Resource Laboratory, Auburn University, Al, USA for the figures in our paper. We are grateful to Philip Morris External Research Program for the support of the study.

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  1. Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA

    • Julia Vaglenova
    • , Noemi Pandiella
    • , Nayana Wijayawardhane
    • , Tiru Vaithianathan
    • , Sandjay Birru
    • , Charles Breese
    • , Vishnu Suppiramaniam
    •  & Clark Randal

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Correspondence to Julia Vaglenova.

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https://doi.org/10.1038/sj.npp.1301496

DISCLOSURE/CONFLICT OF INTEREST

The author(s) declare that, except for income received from their primary employer and funding provided by Philip Morris USA Inc. and Philip Morris External Research Program for the study, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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