Dissertation/Thesis Abstract

Regulation of Basal and Ethanol Abstinence-Induced Affective Behaviors by GluN2B-Containin NMDA Receptors in the Bed Nucleus of the Stria Terminalis and Endocannabinoids
by Holleran, Katherine M., Ph.D., Vanderbilt University, 2016, 193; 13835070
Abstract (Summary)

Administration of a single low dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been demonstrated to elicit long-lasting antidepressant effects in humans with depression, as well as in rodent models of depression. Although pharmacological studies have implicated the GluN2B subunit of the NMDA receptor in these effects, drugs targeting this subunit have off-target actions, and systemic administration of these compounds does not allow for delineation of specific brain regions involved. In this study, we assessed the role of GluN2B in the bed nucleus of the stria terminalis (BNST) in novelty-induced hypophagia (NIH) in mice. First, we verified that ketamine, as well as the GluN2B antagonist Ro25-6981, decreased the latency to consume food in a novel environment in a version of the NIH test. We then hypothesized that GluN2B-containing receptors within the BNST may be a target of systemic ketamine and contribute to behavioral effects. Through the combination of a GluN2B floxed mouse line and stereotaxic delivery of lentiviral Cre recombinase, we found that targeted knockdown of this subunit within the BNST mimicked the reduction in affective behavior observed with systemic ketamine or Ro25-6981 in the NIH test. These data suggest a role for GluN2B-containing NMDARs within the BNST in the affective effects of systemic ketamine.

Indexing (document details)
Advisor: Patel, Sachin
Commitee: Muglia, Louis, Patel, Sachin, Stanwood, Gregg, Winder, Danny
School: Vanderbilt University
Department: Neuroscience
School Location: United States -- Tennessee
Source: DAI-B 80/06(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Neurosciences
Keywords: Alcoholism, BNST, Depression, GluNZB, Ketamine, NMDAR
Publication Number: 13835070
ISBN: 978-0-438-82163-7
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