title: Effects of the cannabinoid 1 receptor peptide ligands hemopressin, (m)RVD-hemopressin(α) and (m)VD-hemopressin(α) on memory in novel object and object location recognition tasks in normal young and Aβ1-42-treated mice.
abstract: The cannabinoid system plays an important role in memory processes, many studies have indicated that cannabinoid receptor ligands have ability to modulate memory in rodents. A nonapeptide hemopressin (Hp) derived from rat brain, acts as a peptide antagonist or selective inverse peptide agonist of cannabinoid 1 (CB1) receptor. N-terminally extended forms of Hp isolated from mouse brain, (m)RVD-hemopressin(α) (RVD) and (m)VD-hemopressin(α) (VD) also bind CB1 receptor, however, as peptide agonists. Here, we investigated the roles of Hp, RVD, and VD on memory in mice using novel object recognition (NOR) and object location recognition (OLR) tasks. In normal young mice, intracerebroventricular (i.c.v.) infusion of Hp before training not only improved memory formation, but also prolonged memory retention in the tasks, these effects could be inhibited by RVD or VD at the same dose and intraperitoneal (i.p.) injection of a small molecule agonist of CB1 receptor WIN55, 212-2 15min before administration of Hp inhibited the memory-improving effect of Hp. In addition, under the same experimental conditions, i.c.v. RVD or VD displayed memory-impairing effects, which could be prevented by Hp (i.c.v.) or AM251 (i.p.), a small molecule antagonist of CB1 receptor. Infusion of amyloid-β (1-42) (Aβ1-42) 14days before training resulted in impairment of memory in mice which could be used as animal model of Alzheimer's disease (AD). In these mice, RVD or VD (i.c.v.) reversed the memory impairment induced by Aβ1-42, and the effects of RVD and VD could be suppressed by Hp (i.c.v.) or AM251 (2mg/kg, i.p.). Separate administration of Hp had no effect in Aβ1-42-treated mice. The above results suggested that Hp, RVD and VD, as CB1 receptor peptide ligands, may be potential drugs to treatment of the memory deficit-involving disease, just as AD.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China; Department of Biochemistry and Molecular Biology, School of Basic Medicine, Xi'an Medical University, Xi'an, China.
authors.forename: Rui-San
authors.initials: RS
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: He
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Jin
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D021641:Recognition, Psychology / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D006454:Hemoglobins; D009025:Morpholines; D009281:Naphthalenes; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; C000590773:RVD-hemopressin, human; D043884:Receptor, Cannabinoid, CB1; C586692:VDPVNFKLLSH-OH; C075222:amyloid beta-protein (1-42); C473218:hemopressin; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
keywords: (m)RVD-hemopressin(α); (m)VD-hemopressin(α); Alzheimer’s disease; Cannabinoid receptor; Hemopressin; Recognition memory