Altered GABA(A)-benzodiazepine receptor number and pharmacology in the adult guinea pig cerebral cortex after chronic prenatal ethanol exposure

Background: The effects of chronic prenatal ethanol exposure on GABA(A)-ben zodiazepine receptor number and binding pharmacology were examined in the c erebral cortex of the postnatal guinea pig. Methods: [H-3]Flunitrazepam binding to GABA(A)-benzodiazepine receptors was measured in a cerebral cortical cell membrane preparation obtained at post natal days 11 (preweaning), 21 (postweaning), and 61 (adulthood). Zolpidem, a GABA(A)-benzodiazepine type 1 receptor-selective ligand, was used in a [ H-3]flunitrazepam competition study. 3 alpha-Hydroxy-5 alpha-pregnan-20-one (allopregnanolone) potentiation of [H-3]muscismol [H-3]flunitrazepam bindi ng, and GABA potentiation of [H-3]flunitrazepam binding were measured in th ese same animals. Results: At postnatal day 61, but not at the younger ages studied, the foll owing was observed: (1) [H-3]Flunitrazepam binding exhibited an increased r eceptor number (B-max) and decreased affinity (increased K-D) in the ethano l-treated offspring compared with isocaloric-sucrose (with pair-feeding) an d water-treated controls: and (2) the relative proportion of GABA(A)-benzod iazepine receptors that had high-affinity binding sites for zolpidem was de creased in the ethanol-treated offspring by 31% and 38% compared with the i socaloric-sucrose/pair-fed and water-treated controls, respectively. Chroni c prenatal ethanol exposure did not alter the efficiency of coupling betwee n GABA, benzodiazepine, and neurosteroid binding sires at any postnatal age s studied. Conclusions: These results suggest that, in the cerebral cortex of the adul t guinea pig, chronic prenatal exposure to ethanol results in increased GAB A(A)-benzodiazepine receptor number, decreased affinity for flunitrazepam, and decreased relative proportion of the GABA(A)-benzodiazepine type 1 rece ptor.