title: Reduced ethanol drinking following selective cortical interneuron deletion of the GluN2B NMDA receptors subunit.
abstract: N-Methyl-d-aspartate receptors (NMDAR) are involved in the regulation of alcohol drinking, but the contribution of NMDAR subunits located on specific neuronal populations remains incompletely understood. The current study examined the role of GluN2B-containing NMDARs expressed on cortical principal neurons and cortical interneurons in mouse ethanol drinking. Consumption of escalating concentrations of ethanol was measured in mice with GluN2B gene deletion in either cortical principal neurons (GluN2BCxNULL) or interneurons (GluN2BInterNULL), using a two-bottle choice paradigm. Results showed that GluN2BInterNULL, but not GluN2BCxNULL, mice consumed significantly less ethanol, at relatively high concentrations, than non-mutant controls. In a second paradigm in which mice were offered a 15% ethanol concentration, without escalation, GluN2BCxNULLmice were again no different from controls. These findings provide novel evidence for a contribution of interneuronal GluN2B-containing NMDARs in the regulation of ethanol drinking.
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Electronic address: aradke@miamioh.edu.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Radke
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Jury
authors.affiliation: Departments of Anesthesiology and Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Delpire
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.
authors.forename: Kazu
authors.initials: K
authors.lastname: Nakazawa
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D017353:Gene Deletion; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D021122:Protein Subunits / Q000172:deficiency* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics
chemical_list: C121001:NR2B NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol
keywords: Addiction; Alcohol; Cortex; Glutamate; Interneuron