Modification of the Effects of Benzodiazepines on the Exploratory Behaviors of Mice on a Hole-Board by Diabetes

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Abstract
The effect of diabetes on the emotional behavior of mice was examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity; i.e., total locomotor activity, numbers and duration of rearing and head-dipping, and latency to the first head-dipping. The number and duration of head-dipping in diabetic mice were less than those in non-diabetic mice. Diazepam (0.1 - 0.56 mg/kg, i.p.) dose-dependently increased the number and duration of head-dipping at doses that did not produce sedation in both diabetic and non-diabetic mice. In contrast, methyl-β-carboline-3-carboxylate (1 and 2 mg/kg, i.p.) decreased the number and duration of head-dipping in non-diabetic mice, but not in diabetic mice. The number and duration of head-dipping in diabetic mice were increased by treatment with flumazenil (0.1 and 0.3 mg/kg, i.v.). These doses of flumazenil did not affect the number or duration of head-dipping in non-diabetic mice. The present data indicate that diabetic mice exhibited anxiety in the hole-board test and that a benzodiazepine receptor antagonist affected the attenuated number and duration of head-dipping in diabetic mice. The heightened anxiety in diabetic mice may be due to the dysfunction of the benzodiazepine receptor and/or of central inhibitory systems.

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