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Loss of ?-GABAA receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure.

ABSTRACT: Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28-42 on ?-aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealed a developmental increase in the GABAA receptor-mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE-exposed rats, the amplitude of the tonic current was significantly reduced compared with controls when tested at postnatal days 45, 60 and 90-120. This AIE-induced reduction in tonic current was found to reflect attenuation of currents mediated by ?-subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE-exposed adult rats compared with control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by ?-GABAA receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of ?-GABAA subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in ?-GABAA tonic currents in the adult prelimbic cortex that may contribute to deficits in decision-making and behavioral control in adulthood.

SUBMITTER: Centanni SW

PROVIDER: S-EPMC4958607 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Loss of δ-GABA<sub>A</sub> receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure.

Centanni Samuel W SW Burnett Elizabeth J EJ Trantham-Davidson Heather H Chandler L Judson LJ

Addiction biology 20160124 3

Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28-42 on γ-aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealed ...[more]

PMID: 26804056

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Dataset Information

Loss of ?-GABAA receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure.

Publications

Loss of δ-GABA<sub>A</sub> receptor-mediated tonic currents in the adult prelimbic cortex following adolescent alcohol exposure.

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