Long-lasting teratogenic effects of nicotine on cognition: gender specificity and role of AMPA receptor function.

Nicotine, the main psychoactive ingredient in tobacco, readily crosses the placental barrier to cause growth and neurobehavioral abnormalities in the offspring. The current study was designed to assess whether nicotinic action causes long lasting teratogenic effects and synaptic dysfunctions. Pregnant Sprague-Dawley rats were infused with nicotine via osmotic minipumps at a dose of 6 mg/kg/day corresponding to the dose receiving during heavy smoking.

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.

Aniracetam reversed learning and memory deficits following prenatal ethanol exposure by modulating functions of synaptic AMPA receptors.

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.

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.

An assessment of the long-term developmental and behavioral teratogenicity of prenatal nicotine exposure.

Maternal tobacco use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of developmental and behavioral deficits in children and adolescents. In the present study, the effects of prenatal nicotine exposure (infused at 6mg/kg/day) and maternal withdraw during neonatal development, was examined in Sprague-Dawley rats on an array of behavioral tasks during different stages of ontogenesis. Offspring of both genders were monitored for exploratory, locomotor, and novelty-seeking activity, anxiety, and learning and memory in an active-avoidance task.