Orexin-A induces anxiety-like behavior through interactions with glutamatergic receptors in the bed nucleus of the stria terminalis of rats

Elizabeth A. Lungwitz, Andrei Molosh, Philip L. Johnson, Brian P. Harvey, Rachel C. Dirks, Amy Dietrich, Pamela Minick, Anantha Shekhar, William A. Truitt

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The hypothalamic neuropeptide orexin (ORX) has been implicated in anxiety, and anxiety-like behaviors. The purpose of these studies was to determine the role of ORX, specifically orexin-A (ORX-A) in the bed nucleus of the stria terminalis (BNST) on anxiety-like behaviors in rats. Rats injected with ORX-A into the BNST displayed greater anxiety-like measures in the social interaction and elevated plus maze tests compared to vehicle treated controls. Such anxiety-like behaviors were not observed when the ORX-A injections were adjacent to the BNST, in the medial septum. The anxiety-inducing effects of direct infusions of ORX-A into the BNST may be a consequence of increased activation of BNST neurons. In BNST slice preparations using patch-clamp techniques, ORX-A induced membrane depolarization and generation of action potentials in a subset of BNST neurons. The anxiety-inducing effects of ORX-A in the BNST also appear to be dependent on NMDA-type glutamate receptor activity, as pre-injecting the NMDA antagonist AP5 into the BNST blocked anxiogenic effects of local ORX-A injections. Injections of AMPA-type receptor antagonists into the BNST prior to ORX-A resulted in only a partial attenuation of anxiety-like behaviors.

Original languageEnglish (US)
Pages (from-to)726-732
Number of pages7
JournalPhysiology and Behavior
Volume107
Issue number5
DOIs
StatePublished - Dec 5 2012

Keywords

  • Anxiety
  • Bed nucleus of the stria terminalis
  • Neuropeptide

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Experimental and Cognitive Psychology
  • Philosophy

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