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

Abstract

Abstract 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 μm of DHH-B significantly increased 36Cl− influx in the absence of muscimol. In the presence of 25 μm muscimol, the addition of 1 μm DHH-B led to significant enhancement of 36Cl− uptake, while 30 μm DHH-B was required to further stimulate the 36Cl− uptake induced by 250 μm muscimol. The results of these studies confirm that DHH-B is a potent anxiolytic-like agent and that GABAA receptor-gated Cl−-channel complex is involved in the anxiolytic-like efficacy of DHH-B.