title: Early alcohol exposure disrupts visual cortex plasticity in mice.
abstract: There is growing evidence that deficits in neuronal plasticity underlie the cognitive problems seen in fetal alcohol spectrum disorders (FASD). However, the mechanisms behind these deficits are not clear. Here we test the effects of early alcohol exposure on ocular dominance plasticity (ODP) in mice and the reversibility of these effects by phosphodiesterase (PDE) inhibitors. Mouse pups were exposed to 5 g/kg of 25% ethanol i.p. on postnatal days (P) 5, 7 and 9. This type of alcohol exposure mimics binge drinking during the third trimester equivalent of human gestation. To assess ocular dominance plasticity animals were monocularly deprived at P21 for 10 days, and tested using optical imaging of intrinsic signals. During the period of monocular deprivation animals were treated with vinpocetine (20mg/kg; PDE1 inhibitor), rolipram (1.25mg/kg; PDE4 inhibitor), vardenafil (3mg/kg; PDE5 inhibitor) or vehicle solution. Monocular deprivation resulted in the expected shift in ocular dominance of the binocular zone in saline controls but not in the ethanol group. While vinpocetine successfully restored ODP in the ethanol group, rolipram and vardenafil did not. However, when rolipram and vardenafil were given simultaneously ODP was restored. PDE4 and PDE5 are specific to cAMP and cGMP respectively, while PDE1 acts on both of these nucleotides. Our findings suggest that the combined activation of the cAMP and cGMP cascades may be a good approach to improve neuronal plasticity in FASD models.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Lantz
authors.forename: Weili
authors.initials: W
authors.lastname: Wang
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Medina
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D023882:Dominance, Ocular / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010775:Photic Stimulation; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D012683:Sensory Deprivation; D013450:Sulfones / Q000494:pharmacology; D016019:Survival Analysis; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride; D014748:Vinca Alkaloids / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects* / Q000254:growth & development*; D014795:Visual Pathways / Q000187:drug effects / Q000254:growth & development
chemical_list: D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014748:Vinca Alkaloids; D000431:Ethanol; C013983:vinpocetine; D000069058:Vardenafil Dihydrochloride