title: Altered GABA(A)-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure.
abstract: BACKGROUND
  The effects of chronic prenatal ethanol exposure on GABA(A)-benzodiazepine receptor number and binding pharmacology were examined in the cerebral cortex of the postnatal guinea pig.
  
  
  METHODS
  [3H]Flunitrazepam binding to GABA(A)-benzodiazepine receptors was measured in a cerebral cortical cell membrane preparation obtained at postnatal days 11 (preweaning), 21 (postweaning), and 61 (adulthood). Zolpidem, a GABA(A)-benzodiazepine type 1 receptor-selective ligand, was used in a [3H]flunitrazepam competition study. 3a-Hydroxy-5alpha-pregnan-20-one (allopregnanolone) potentiation of [3H]muscimol and [3H]flunitrazepam binding, and GABA potentiation of [3H]flunitrazepam binding were measured in these same animals.
  
  
  RESULTS
  At postnatal day 61, but not at the younger ages studied, the following was observed: (1) [3H]Flunitrazepam binding exhibited an increased receptor number (Bmax) and decreased affinity (increased K(D)) in the ethanol-treated offspring compared with isocaloric-sucrose (with pair-feeding) and water-treated controls; and (2) the relative proportion of GABA(A)-benzodiazepine receptors that had high-affinity binding sites for zolpidem was decreased in the ethanol-treated offspring by 31% and 38% compared with the isocaloric-sucrose/pair-fed and water-treated controls, respectively. Chronic prenatal ethanol exposure did not alter the efficiency of coupling between GABA, benzodiazepine, and neurosteroid binding sites at any postnatal ages studied.
  
  
  CONCLUSIONS
  These results suggest that, in the cerebral cortex of the adult guinea pig, chronic prenatal exposure to ethanol results in increased GABA(A)-benzodiazepine receptor number, decreased affinity for flunitrazepam, and decreased relative proportion of the GABA(A)-benzodiazepine type 1 receptor.
authors.affiliation: Department of Pharmacology and Toxicology and the Department of Anaesthesia and Critical Care, Queen's University, Kingston, Ontario, Canada.
authors.forename: C D
authors.initials: CD
authors.lastname: Bailey
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
authors.forename: J N
authors.initials: JN
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D018757:GABA Modulators; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D000431:Ethanol; D005445:Flunitrazepam