Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling.

摘要: Extracts of Cannabis sativa have been used for their calming and sedative effects centuries. Recent developments in drug discovery suggested that modulation neuronal endogenous cannabinoid signaling systems could represent a novel approach to the treatment anxiety-related disorders while minimizing adverse direct acting receptor agonists. In this study, we evaluated agonists antagonists endocannabinoid-modulating drugs on anxiety-like behavior mice using elevated-plus maze. We found CB1 (1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP 55,940) (0.001-0.3 mg/kg) 2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate) (WIN 55212-2) (0.3-10 increased time spent open arms (To) at low doses only. At highest tested, both compounds altered overall locomotor activity. contrast, Delta9-tetrahydrocannabinol (0.25-10 produced dose-dependent reduction To. The endocannabinoid uptake/catabolism inhibitor 4-hydroxyphenylarachidonylamide (AM404) an increase To had no effect dose tested. fatty acid amide hydrolase cyclohexyl carbamic 3'-carbamoyl-biphenyl-3-yl ester (URB597) (0.03-0.3 monophasic, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716) (1-10 N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-related decreases These data indicate activation receptors reduces behaviors further support anxiolytic role signaling. results suggest pharmacological system new psychiatric disorders.