Orexin-A induces anxiety-like behavior through interactions with glutamatergic receptors in the bed nucleus of the stria terminalis of rats.
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.
Graduate Program in Medical Neuroscience, Indiana Clinical and Translational Sciences Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Elizabeth A
EA
Lungwitz
Andrei
A
Molosh
Philip L
PL
Johnson
Brian P
BP
Harvey
Rachel C
RC
Dirks
Amy
A
Dietrich
Pamela
P
Minick
Anantha
A
Shekhar
William A
WA
Truitt
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects* / Q000502:physiology; D012919:Social Behavior
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D017470:Receptors, Glutamate