Yokukansan inhibits morphine tolerance and physical dependence in mice: The role of α2A -adrenoceptor

• Published in: Neuroscience Vol. 227; pp. 336 - 349
• Main Authors: Nakagawa, T, Nagayasu, K, Nishitani, N, Shirakawa, H, Sekiguchi, K, Ikarashi, Y, Kase, Y, Kaneko, S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 27.12.2012; Elsevier
• Subjects: Adrenergic Agents - pharmacology; Adrenergic alpha-Antagonists - pharmacokinetics; Adrenergic beta-Antagonists - pharmacology; Analgesics; Analysis of Variance; Animals; Behavior, Addictive - drug therapy; Biological and medical sciences; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Tolerance; Drugs, Chinese Herbal - therapeutic use; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacokinetics; Guanosine Diphosphate - pharmacology; Isotopes - pharmacokinetics; Male; Medical sciences; Mice; morphine; Morphine Dependence - drug therapy; Neurology; Neuropharmacology; Norepinephrine Plasma Membrane Transport Proteins - metabolism; Pain Threshold - drug effects; Pharmacology. Drug treatments; physical dependence; Propranolol - pharmacology; Protein Binding - drug effects; Radioligand Assay; Receptors, Adrenergic, alpha-2 - metabolism; Time Factors; tolerance; Tropanes - pharmacokinetics; yokukansan; α2-adrenoceptor; Asia; Japan; BPSD; YKS; BBB; MPE; guanosine-5′-diphosphate; HRP; CHO; locus coeruleus; AUC; GDP; blood–brain barrier; UH; Uncaria hook; Glycyrrhiza; ethylenediaminetetraacetic acid; horseradish peroxidase; MDCK; GME; tolerance; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; ethyleneglycol- bis(β-aminoethyl)- N, N, N′, N′-tetraacetic acid; SDS; geissoschizine methyl ether; EGTA; AR; Chinese hamster ovary; norepinephrine transporter; α 2-adrenoceptor; Madin–Darby canine kidney; adrenoceptor; IC 50; maximal possible effect; half maximal inhibitory concentration; morphine; yokukansan; GTPγS; analysis of variance; ANOVA; sodium dodecyl sulfate; physical dependence; guanosine-5′- O-(3-thiotriphosphate); peroral; area under the curve; GR; EDTA; p.o; behavioral and psychological symptoms of dementia; HEPES; LC; NET; IC50; α2-adrenoceptor; α2-Adrenergic receptor; Rodentia; Tolerance; Opiates; Morphine; Narcotic analgesic; α; Vertebrata; Mammalia; Folk medicine; Mouse; α2A-adrenergic receptor; Animal; Dependence
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2012.09.079

Highlights ► Yokukansan (YKS) is a traditional Japanese herbal medicine clinically used for BPSD. ► Repeated administration of YKS inhibits morphine tolerance and physical dependence. ► The inhibition is due to prevention of decrease in α2A -AR by its prolonged blockade. ► YKS and its chemical constituents show antagonist activity against α2A -AR. ► The active constituents are responsible for the inhibitory effect of YKS.