Altered GABAA-Benzodiazepine Receptor Number and Pharmacology in the Adult Guinea Pig Cerebral Cortex After Chronic Prenatal Ethanol Exposure

doi:10.1111/j.1530-0277.1999.tb04078.x

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Wiley InterScience

Alcoholism: Clinical and Experimental Research

Volume 23 Issue 11, Pages 1816 - 1824

Published Online: 30 May 2006

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Altered GABA_A-Benzodiazepine Receptor Number and Pharmacology in the Adult Guinea Pig Cerebral Cortex After Chronic Prenatal Ethanol Exposure

Craig D.C. Bailey ¹ , James F. Brien ¹ James N. Reynolds ¹

¹ Department of Pharmacology and Toxicology and the Department of Anaesthesia and Critical Care, Queen's University, Kingston, Ontario, Canada.

Correspondence to Reprint requests: James N. Reynolds. Ph.D., Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada K7L 3N6; Fax: 613-533-6412; E-mail: jnr@posi.queensu.ca

Funding for this research was provided by the Medical Research Council of Canada Operating Grant MT-15150. C.D.C.B. is the holder of an Ontario Graduate Scholarship.

The authors are indebted to Mr. Rajan Puri, Mr. Neil Butters, and Mr. Malcolm Gibson for their assistance in chronic animal treatment.

KEYWORDS

GABA_A Receptor • Cerebral Cortex • Guinea Pig • Prenatal Ethanol Exposure • Benzodiazepine

ABSTRACT

: 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 compctition study. 3α-Hydroxy-5α-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 (B_max) 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.

Received for publication July 6, 1999; accepted September 14, 1999.

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1530-0277.1999.tb04078.x About DOI