• Neuroscience letters · Aug 2014

    Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice.

    • Jia-Xin Pan, Zi-Long Wang, Ning Li, Zheng-Lan Han, Xu-Hui Li, Hong-Hai Tang, Pei Wang, Ting Zheng, Quan Fang, and Rui Wang.
    • Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou 730000, PR China.
    • Neurosci. Lett. 2014 Aug 22;578:187-91.

    AbstractThe nonapeptide hemopressin and its N-terminal extension VD-hemopressin(α) were reported as an antagonist/inverse agonist and an agonist of CB1 receptor, respectively. These novel cannabinoid peptides have been demonstrated to modulate the acute pain. In the present study, hemopressin (11, 22 and 45 nmol, i.c.v.) dose-dependently produced antinociception after supraspinal administration in the radiant heat tail-flick test. Furthermore, the development of antinociceptive tolerance to hemopressin, VD-hemopressin(α) and WIN55,212-2, and cross-tolerance among these cannabinoids were investigated in mice. The tolerance developed on day 4 after supraspinal injection of hemopressin (45 nmol), VD-hemopressin(α) (20 nmol) and WIN55,212-2 (7.5 nmol). Our results indicated symmetrical cross-tolerance between hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice. These results demonstrate that both hemopressin and VD-hemopressin(α) have a time-course and extent of tolerance similar to the synthetic cannabinoid WIN55,212-2. In addition, our data imply that a common mechanism is involved in the antinociception of the three cannabinoid ligands.Copyright © 2014. Published by Elsevier Ireland Ltd.

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