Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity.
Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational approach for the treatment of alcohol-related cognitive deficits using aniracetam, an allosteric AMPAR modulator. In the present study, 28 to 34-day-old rats exposed to ethanol in utero were treated with aniracetam, and subsequently exhibited persistent improvement in mEPSC amplitude, frequency, and decay time. Furthermore, these animals expressed positive changes in synaptic single channel properties, suggesting that aniracetam ameliorates prenatal ethanol-induced deficits through modifications at the single channel level. Specifically, single channel open probability, conductance, mean open and closed times, and the number and burst duration were positively affected. Our findings emphasize the utility of compounds which slow the rate of deactivation and desensitization of AMPARs such as aniracetam.
Wijayawardhane
Nayana
N
Department of Pharmacal Sciences, 401 Walker Building, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
Shonesy
Brian C
BC
Vaithianathan
Thirumalini
T
Pandiella
Noemi
N
Vaglenova
Julia
J
Breese
Charles R
CR
Dityatev
Alexander
A
Suppiramaniam
Vishnu
V
D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D013997:Time Factors
D002492:Central Nervous System Depressants; D018683:Excitatory Amino Acid Agents; D018697:Nootropic Agents; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D000431:Ethanol; C036466:aniracetam