title: Loss of δ-GABAAreceptor-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 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 a developmental increase in the GABAAreceptor-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 δ-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 δ-GABAAreceptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of δ-GABAAsubunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in δ-GABAAtonic currents in the adult prelimbic cortex that may contribute to deficits in decision-making and behavioral control in adulthood.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Centanni
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Burnett
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Trantham-Davidson
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: L Judson
authors.initials: LJ
authors.lastname: Chandler
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid
keywords: Adolescence; GABAA receptors; alcohol; prefrontal cortex; pyramidal; tonic current