Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats.
BACKGROUND
Anatomical studies have shown that the paraventricular nucleus of the thalamus (PVT) innervates areas of the forebrain involved in the expression and regulation of emotional behaviors including fear and anxiety. In addition, the PVT is densely innervated by fibers containing orexin-A (OXA) and orexin-B (OXB), peptides that are well-known for their arousal effects on behavior.


OBJECTIVE
In this study, we investigate whether microinjections of orexin receptor agonists and antagonists in the PVT region alter expression of anxiety-like behaviors in the rat as measured in the elevated plus maze.


RESULTS
We report that microinjections of OXA and OXB in the PVT region elicited anxiety-like response as indicated by a reduction in open arm time and entries. In addition, OXA and OXB produced changes in ethological measures indicative of an anxiety state. Central administrations of antagonists for corticotropin releasing factor (CRF) or the opioid kappa receptors attenuated the anxiogenic effects produced by microinjections of OXA in the PVT region. We also provide evidence that endogenously released orexins act at the PVT to produce anxiety by showing that microinjections of TCSOX229, an orexin-2 receptor antagonist, in the PVT region attenuated the anxiogenic effects produced by a previous exposure to footshock stress.


CONCLUSIONS
This study indicates that endogenously released orexins act on the PVT to regulate anxiety levels through mechanisms involving the brain kappa and CRF receptors.
Li
Yonghui
Y
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Li
Sa
S
Wei
Chuguang
C
Wang
Huiying
H
Sui
Nan
N
Kirouac
Gilbert J
GJ
D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D020644:Midline Thalamic Nuclei / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000633:toxicity; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D017473:Receptors, Opioid, kappa; D003346:Corticotropin-Releasing Hormone