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Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced antinociceptive effect in formalin test

Azhdari-Zarmehri, Hassan and Esmaeili, Mohammad-Hossein and sofiabadi, mohammad and Haghdoost-Yazdi, Hashem (2013) Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced antinociceptive effect in formalin test. Pharmacology, Biochemistry and Behavior Journal.

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Abstract

Orexin-A and orexin-B are two neuropeptides selectively synthesized in the lateral hypothalamus (LH), a region involved in morphine induced analgesia and pain modulation. Furthermore, orexin-A has been reported to produce an analgesic effect in pain models, which was blocked by orexin-1 receptor antagonist SB-334867, but not naloxone. We studied the effects of intracerebroventricular (ICV) injection of SB-334867, a selective orexin receptor type-1 antagonist, onmorphine-induced antinociceptive effect in formalin test in rats.Morphine injection at a dose of 1.5mg/kg caused a significant decrease in the formalin-induced nociceptive behaviors in phase 1, interphase, and phase 2A, whereas at doses of 3, 6, and 10mg/kg, a significant reduction in the formalin-induced nociceptive behaviors was observed in all phases. The ICV injection of SB-334867 alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatmentwith SB-334867 at a dose of 0.5nmol significantly attenuated the analgesia induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at dose 3mg/kg of morphine just phase 2B of formalin test). Also, pre-treatmentwith SB-334867 at a dose of 5nmol considerably attenuated the morphine-induced analgesia (at dose 1.5mg/kg of morphine; phase 1, interphase, and phase 2, at dose 3 and 6mg/kg ofmorphine just phase 2 of formalin test). Pre-treatmentwith SB-334867 at a dose of 50 nmol remarkably attenuated the morphine-induced analgesia (at dose 1.5 and 3 mg/kg of morphine; in phase 1, interphase, and phase 2 and also at dose 6 mg/kg of morphine; phase 1 and phase 2B of formalin test). These data suggest that the antinociceptive effects of morphine in formalin test might be associated with orexin receptor type-1. Our findings reveal a new role for the lateral hypothalamus orexin neurons in the morphine-induced analgesia.

Item Type: Article
Subjects: Q Science > QP Physiology
Divisions: University Portal > research center > camr
Depositing User: pr Camr research
Date Deposited: 16 Sep 2015 05:33
Last Modified: 16 Sep 2015 05:33
URI: http://eprints.qums.ac.ir/id/eprint/2599

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