title: Aniracetam reversed learning and memory deficits following prenatal ethanol exposure by modulating functions of synaptic AMPA receptors.
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 (alpha-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.
authors.affiliation: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. vagleju@auburn.edu
authors.forename: Julia
authors.initials: J
authors.lastname: Vaglenova
authors.forename: Noemi
authors.initials: N
authors.lastname: Pandiella
authors.forename: Nayana
authors.initials: N
authors.lastname: Wijayawardhane
authors.forename: Tiru
authors.initials: T
authors.lastname: Vaithianathan
authors.forename: Sandjay
authors.initials: S
authors.lastname: Birru
authors.forename: Charles
authors.initials: C
authors.lastname: Breese
authors.forename: Vishnu
authors.initials: V
authors.lastname: Suppiramaniam
authors.forename: Clark
authors.initials: C
authors.lastname: Randal
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D018697:Nootropic Agents / Q000627:therapeutic use*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D012737:Sex Factors; D013569:Synapses / Q000187:drug effects*
chemical_list: D018697:Nootropic Agents; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D000431:Ethanol; C036466:aniracetam