alexa Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell.


Journal of Addiction Research & Therapy

Author(s): Sharf R, Sarhan M, Dileone RJ

Abstract Share this page

Abstract BACKGROUND: The lateral hypothalamic neuropeptide orexin (or hypocretin) is implicated in drug addiction. Although a role for orexin has been shown in reward and dependence, the molecular and neural mechanisms are unclear. We investigated the mechanism and neuroanatomic basis of orexin's role in morphine withdrawal. METHODS: C57BL/6J mice received chronic morphine followed by naloxone (0 or 1 mg/kg, subcutaneous) to precipitate withdrawal. Before naloxone, mice received SB-334867 (0 or 20 mg/kg, intraperitoneal), an orexin 1 receptor (Ox1r) antagonist. Using immunohistochemistry, c-Fos, a marker of cell activation, was quantified in the nucleus accumbens (Acb), lateral hypothalamus (LH), ventral tegmental area (VTA), and locus coeruleus (LC). Retrograde tracing with fluorogold (FG) was performed to determine whether orexin neurons project directly to the Acb. RESULTS: SB-334867 before naloxone significantly attenuated withdrawal symptoms. Withdrawal was accompanied by an increase in c-Fos expression in the Acb shell (AcbSh), which was reduced by SB-334867 but had no effect on the VTA or the LC. Morphine withdrawal increased c-Fos expression in the dorsomedial (DMH) and perifornical (PFA) regions but not in the lateral region of the LH (LLH). Orexin neurons do not appear to form direct connections with Acb neurons. CONCLUSIONS: Altogether, these data demonstrate that orexin, acting via Ox1r, is critical for the expression of morphine withdrawal. AcbSh activation during withdrawal is dependent on Ox1r function and is likely mediated by indirect action of LH orexin neurons.
This article was published in Biol Psychiatry and referenced in Journal of Addiction Research & Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version