The mechanism of alteration of monoamine metabolism in brain regions in marble burying behavior-isolated housing mice and effect of Oren-gedoku-to on this alteration

Abstract

The mechanism of the alteration in marble burying behavior-isolated housing (MBB-IH) mice was investigated. The determination of hypothalamus monoamine and serum corticosterone contents indicated that MBB-IH mice readily responded to the stress stimuli in conditioned fear stress. Six drugs, such as buspirone (10 mg/kg, p.o.), Zimelidine (10 mg/kg, p.o.) clomipramin (10 mg/kg, p.o.), yohimbine (5 mg/kg, p.o.), ethyl β-carboline- 3-carboxylate (β-CCE, 5 mg/ kg, p.o.) and flumazenil (15 mg/kg, p.o.) were singly and/or three times administered to MBB-IH mice. Their inhibitory activity on the MBB-IH mice was considered by the use of activity profiles consisting of spontaneous locomotor activity, marble burying behavior and hypothalamus monoamine content. Using these profiles, we calculated the activities as vector in three-dimensional space, and compared the distance from the control point (DCP). DCP(DOPAC) and DCP(5-HIAA) were shortened by single administration of β-CCE and flumazenil. Oren-gedoku-to (30 and 300 mg/kg, p.o.) shortened the DCP(DOPAC) and DCP(5-HIAA) similarly to β-CCE. The blended crude drugs in Oren-gedoku-to, Coptis rhizome (636.0 mg/kg, p.o.), Scutellaria root (644.4 mg/kg, p.o.) and Gardenia fruit (894.8 mg/kg, p.o.) shortened the DCP(DOPAC). Coptis rhizome and Scutellaria root also shortened the DCP(5-HIAA). These results suggest that GABA neuron function intensely affects the alteration of MBB-IH and Oren-gedoku-to has the intrinsic benzodiazepine-like activity.