title: Acute administration of vinpocetine, a phosphodiesterase type 1 inhibitor, ameliorates hyperactivity in a mice model of fetal alcohol spectrum disorder.
abstract: BACKGROUND
  Maternal alcohol use during pregnancy causes a continuum of long-lasting disabilities in the offspring, commonly referred to as fetal alcohol spectrum disorder (FASD). Attention-deficit/hyperactivity disorder (ADHD) is possibly the most common behavioral problem in children with FASD and devising strategies that ameliorate this condition has great clinical relevance. Studies in rodent models of ADHD and FASD suggest that impairments in the cAMP signaling cascade contribute to the hyperactivity phenotype. In this work, we investigated whether the cAMP levels are affected in a long-lasting manner by ethanol exposure during the third trimester equivalent period of human gestation and whether the acute administration of the PDE1 inhibitor vinpocetine ameliorates the ethanol-induced hyperactivity.
  
  
  METHODS
  From postnatal day (P) 2 to P8, Swiss mice either received ethanol (5g/kg i.p.) or saline every other day. At P30, the animals either received vinpocetine (20mg/kg or 10mg/kg i.p.) or vehicle 4h before being tested in the open field. After the test, frontal cerebral cortices and hippocampi were dissected and collected for assessment of cAMP levels.
  
  
  RESULTS
  Early alcohol exposure significantly increased locomotor activity in the open field and reduced cAMP levels in the hippocampus. The acute treatment of ethanol-exposed animals with 20mg/kg of vinpocetine restored both their locomotor activity and cAMP levels to control levels.
  
  
  CONCLUSIONS
  These data lend support to the idea that cAMP signaling system contribute to the hyperactivity induced by developmental alcohol exposure and provide evidence for the potential therapeutic use of vinpocetine in FASD.
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Nunes
authors.forename: Kélvia
authors.initials: K
authors.lastname: Ferreira-Rosa
authors.forename: Maurício Dos S
authors.initials: Mdos S
authors.lastname: Pereira
authors.forename: Regina C
authors.initials: RC
authors.lastname: Kubrusly
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.forename: Yael
authors.initials: Y
authors.lastname: Abreu-Villaça
authors.forename: Cláudio C
authors.initials: CC
authors.lastname: Filgueiras
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000473:pathology*; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000097:blood / Q000633:toxicity; D000242:Cyclic AMP / Q000032:analysis; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy*; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D016037:Single-Blind Method; D015996:Survival Rate; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D010726:Phosphodiesterase Inhibitors; D014748:Vinca Alkaloids; D000431:Ethanol; C013983:vinpocetine; D000242:Cyclic AMP