Role of Orexin in the Tolerance and Physical Dependence to Morphine

• Main Authors: Samad Nazemi, Hassan Azhdari zarmrhri, Hashem Haghdoost-Yazdi
• Format: Article
• Language: English
• Published: Babol University of Medical Sciences 2014-12-01
• Series: Majallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Bābul
• Subjects: KEY WORDS:Morphine; Orexin; Tolerance; Dependence.
• Online Access: http://jbums.org/browse.php?a_code=A-10-1453-3&slc_lang=en&sid=1

BACKGROUND AND OBJECTIVE: Although opioid drugs cause analgesia and more effective in treatment of pain but, its utility is hindered by the development of tolerance to its analgesic effects. Orexin A and B (hypocretin 1 and 2) discovered in 1998 and projected to large areas of the brain regions involved in the tolerance and dependence to morphine. The attenuated withdrawal syndrome seen in orexinknock-out mice suggests that such regulation of orexin neurons may be an important contributor to morphine physical dependence and to the expression of withdrawal. METHODS: This systematic review conducted on articles published on orexin from 1998 to 2012 in the following electronic databases: Medline, Pubmed, ISI and Scopus by using keywords including morphine, orexin, tolerance and dependence. FINDINGS: Although morphine-tolerance tended to develop in response to repeated injections of morphine, pre-treatment of OXR1 antagonist prevented this effect, causing a delay in the development of morphine-tolerance. Moreover, co-administration of orexin receptor 1 antagonist with morphine significantly decreased the somatic signs of withdrawal. CONCLUSION:This suggested development of orexin receptor antagonists could prevent the development of tolerance and dependence to morphine.