Sodium valproate decreases exploratory behaviour in mice: development of tolerance and cross-tolerance with chlordiazepoxide

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Abstract

Sodium valproate (400 mg/kg) significantly reduced exploratory head-dipping in mice, without significant reductions in locomotor activity or rearing. After 5 daily injections of sodium valproate (50 or 400 mg/kg) there was tolerance to the effects of a test dose of 400 mg/kg. Pretreatment for 5 days with chlordiazepoxide (5 mg/kg) did not change the effects of sodium valproate (400 mg/kg), but 5 days pretreatment with chlordiazepoxide (20 mg/kg) did not produce cross-tolerance. Sodium valproate (50 mg/kg) was without significant effect acutely, or after 5 days of pretreatment with sodium valproate (50 or 400 mg/kg) or chlordiazepoxide (5 or 20 mg/kg). Daily injections of the benzodiazepine antagonist, flumazenil (10 mg/kg), immediately after the daily injection of sodium valproate (400 mg/kg) or chlordiazepoxide (20 mg/kg) did not prevent the development of tolerance or cross-tolerance. This suggests that benzodiazepine receptors may not mediate these phenomena; possible roles of GABA and 5-HT are also discussed. © 1988.

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File, S. E., & Aranko, K. (1988). Sodium valproate decreases exploratory behaviour in mice: development of tolerance and cross-tolerance with chlordiazepoxide. European Journal of Pharmacology, 151(2), 293–299. https://doi.org/10.1016/0014-2999(88)90811-4

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