Confirmation of the anxiolytic-like effect of dihydrohonokiol following behavioural and biochemical assessments.
Previous studies in this laboratory revealed that dihydrohonokiol-B (DHH-B; 3'-(2 propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol), a partially reduced derivative of honokiol, was an effective anxiolytic-like agent in mice at an oral dose of 0.04 mg kg(-1), and at higher doses, when evaluated by the elevated plus-maze test. The aim of this study was to further confirm the anxiolytic-like effect of DHH-B using an additional behavioural procedure (Vogel's conflict test in mice) and a biochemical assessment (in-vitro determination of muscimol-stimulated 36Cl- uptake into mouse cortical synaptoneurosomes). As in earlier experiments, DHH-B (0.04-1 mg kg(-1), p.o.) was shown to prolong the time spent in the open-sided arms of the elevated plus-maze in a dose-dependent manner. Moreover, in the Vogel's conflict test, DHH-B (5 mg kg(-1), p.o.) significantly increased punished water intake. In tests with mouse cerebral cortical synaptoneurosomes, 10 and 30 microM of DHH-B significantly increased 36Cl- influx in the absence of muscimol. In the presence of 25 microM muscimol, the addition of 1 microM DHH-B led to significant enhancement of 36Cl- uptake, while 30 microM DHH-B was required to further stimulate the 36Cl- uptake induced by 250 microM muscimol. The results of these studies confirm that DHH-B is a potent anxiolytic-like agent and that GABA(A) receptor-gated Cl(-)-channel complex is involved in the anxiolytic-like efficacy of DHH-B.
Maruyama
Y
Y
Department of Neuropsychopharmacology (Tsumura), Gunma University School of Medicine, Maebashi, Japan. yuji@med.gunma-u.ac.jp
Kuribara
H
H
Kishi
E
E
Weintraub
S T
ST
Ito
Y
Y
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology
D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D018118:Chloride Channels; D011963:Receptors, GABA-A; C417822:dihydrohonokiol