Postnatal aniracetam treatment improves prenatal ethanol induced attenuation of AMPA receptor-mediated synaptic transmission.
Aniracetam is a nootropic compound and an allosteric modulator of AMPA receptors (AMPARs) which mediate synaptic mechanisms of learning and memory. Here we analyzed impairments in AMPAR-mediated synaptic transmission caused by moderate prenatal ethanol exposure and investigated the effects of postnatal aniracetam treatment on these abnormalities. Pregnant Sprague-Dawley rats were gavaged with ethanol or isocaloric sucrose throughout pregnancy, and subsequently the offspring were treated with aniracetam on postnatal days (PND) 18 to 27. Hippocampal slices prepared from these pups on PND 28 to 34 were used for the whole-cell patch-clamp recordings of AMPAR-mediated spontaneous and miniature excitatory postsynaptic currents in CA1 pyramidal cells. Our results indicate that moderate ethanol exposure during pregnancy results in impaired hippocampal AMPAR-mediated neurotransmission, and critically timed aniracetam treatment can abrogate this deficiency. These results highlight the possibility that aniracetam treatment can restore synaptic transmission and ameliorate cognitive deficits associated with the fetal alcohol syndrome.
Wijayawardhane
Nayana
N
Department of Pharmacal Sciences, 401 Walker Building, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
Shonesy
Brian C
BC
Vaglenova
Julia
J
Vaithianathan
Thirumalini
T
Carpenter
Mark
M
Breese
Charles R
CR
Dityatev
Alexander
A
Suppiramaniam
Vishnu
V
D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000431:Ethanol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
D002492:Central Nervous System Depressants; D018697:Nootropic Agents; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D000431:Ethanol; D018698:Glutamic Acid; C036466:aniracetam