IngentaConnect Confirmation of the anxiolytic-like effect of dihydrohonokiol fol...

Authors: Maruyama Y.¹; Kuribara H.¹; Kishi E.¹; Weintraub S.T.²; Ito Y.³

Source: Journal of Pharmacy and Pharmacology, Volume 53, Number 5, 1 May 2001 , pp. 721-725(5)

Publisher: Pharmaceutical Press

Abstract:

Previous studies in this laboratory revealed that dihydrohonokiol-B (DHH-B; 3 prime

-(2 propenyl)-5-propyl-(1,1 prime

-biphenyl)-2,4 prime

-diol), a partially reduced derivative of honokiol, was an effective anxiolytic-like agent in mice at an oral dose of 0.04mg 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 (0.04–1mg 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 (5mg kg^-1, p.o.) significantly increased punished water intake. In tests with mouse cerebral cortical synaptoneurosomes, 10 and 30

M of DHH-B significantly increased ³⁶Cl^- influx in the absence of muscimol. In the presence of 25

M muscimol, the addition of 1

M DHH-B led to significant enhancement of ³⁶Cl^- uptake, while 30

M DHH-B was required to further stimulate the ³⁶Cl^- uptake induced by 250

M 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.

Document Type: Research article

DOI: 10.1211/0022357011775848

Affiliations: 1: Department of Neuropsychopharmacology (Tsumura), Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, Japan, 371-8511 2: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, USA, 78284-7760 3: Department of Pharmacology, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi, Chiba, Japan, 274-8555

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Confirmation of the anxiolytic-like effect of dihydrohonokiol following behavioural and biochemical assessments