RT Journal Article SR Electronic T1 Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-Terminally Extended Hemopressin Peptide JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 316 OP 323 DO 10.1124/jpet.113.209866 VO 348 IS 2 A1 Zheng-lan Han A1 Quan Fang A1 Zi-long Wang A1 Xu-hui Li A1 Ning Li A1 Xue-mei Chang A1 Jia-xin Pan A1 Hong-zhu Tang A1 Rui Wang YR 2014 UL http://jpet.aspetjournals.org/content/348/2/316.abstract AB The cannabinoid system has been demonstrated to modulate the acute and chronic pain of multiple origins. Mouse VD-hemopressin(α) [(m)VD-Hpα], an 11-residue α-hemoglobin–derived peptide, was recently reported to function as a selective agonist of the cannabinoid receptor type 1 (CB1) in vitro. To characterize its behavioral and physiological properties, we investigated the in vivo effects of (m)VD-Hpα in mice. In the mouse tail-flick test, (m)VD-Hpα dose-dependently induced antinociception after supraspinal (EC50 = 6.69 nmol) and spinal (EC50 = 2.88 nmol) administration. The antinociceptive effects of (m)VD-Hpα (intracerebroventricularly and intrathecally) were completely blocked by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamide (AM251; CB1 antagonist), but not by 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl(4-methoxyphenyl)-methanone (AM630; CB2 antagonist) or naloxone (opioid antagonist), showing its selectivity to the CB1 receptor. Furthermore, the central nervous system (CNS) effects of (m)VD-Hpα were evaluated in body temperature, locomotor activity, tolerance development, reward, and food intake assays. At the highly antinociceptive dose (3 × EC50), (m)VD-Hpα markedly exerted hypothermia and hypoactivity after supraspinal administration. Repeated intracerebroventricular injection of (m)VD-Hpα resulted in both development of tolerance to antinociception and conditioned place aversion. In addition, central injection of (m)VD-Hpα dose-dependently stimulated food consumption. These findings demonstrate that this novel cannabinoid peptide agonist induces CB1-mediated central antinociception with some CNS effects, which further supports a CB1 agonist character of (m)VD-Hpα. Moreover, the current study will be helpful to understand the in vivo properties of the endogenous peptide agonist of the cannabinoid CB1 receptor.