Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior

Details

Serval ID
serval:BIB_91931E6FEB67
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Boutrel Benjamin, Kenny Paul J., Specio Sheila E., Martin-Fardon Rémi, Markou Athina, Koob George F., Lecea Luis de
ISSN
0027-8424
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
102
Number
52
Pages
19168-19173
Language
english
Notes
SAPHIRID:67381
Abstract
Hypocretin-1 and -2 (Hcrt-1 and Hcrt-2), also referred to as orexin-A and -B, are neuropeptides synthesized by a few thousand neurons in the lateral hypothalamus. Hypocretin-containing neurons project throughout the brain, with a prominent input to basal forebrain structures involved in motivation, reward, and stress. However, the role of hypocretins in addiction-related behaviors remains largely unexplored. Here we show that intracerebroventricular infusions of Hcrt-1 lead to a dose-related reinstatement of cocaine seeking without altering cocaine intake in rats. Hcrt-1 also dramatically elevates intracranial self-stimulation thresholds, indicating that, unlike treatments with reinforcing properties such as cocaine, Hcrt-1 negatively regulates the activity of brain reward circuitries. Hypocretin-induced reinstatement of cocaine seeking was prevented by blockade of noradrenergic and corticotropin-releasing factor systems, suggesting that Hcrt-1 reinstated drug seeking through induction of a stress-like state. Consistent with this interpretation, the selective Hcrt-1 receptor antagonist SB-334867 blocked footshock-induced reinstatement of previously extinguished cocaine-seeking behavior. These findings reveal a previously unidentified role for hypocretins in driving drug seeking through activation of stress pathways in the brain.
Pubmed
Web of science
Open Access
Yes
Create date
11/03/2008 15:07
Last modification date
20/08/2019 15:54
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