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l-Arginine abolishes the anxiolytic-like effect of diazepam in the elevated plus-maze test in rats

Volke, V., Soosaar, A., Kõks, S., Vasar, E. and Männistö, P.T. (1998) l-Arginine abolishes the anxiolytic-like effect of diazepam in the elevated plus-maze test in rats. European Journal of Pharmacology, 351 (3). pp. 287-290.

Link to Published Version: https://doi.org/10.1016/S0014-2999(98)00364-1
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Abstract

The involvement of nitrergic mechanisms in the behavioural effects of diazepam in rats was studied in the elevated plus-maze, open-field and rotarod tests. Administration of the nitric oxide (NO) precursor l-arginine (100 mg/kg, i.p.), assumed to increase the synthesis of NO, abolished the anxiolytic-like effect of diazepam (2 mg/kg, i.p.) in the elevated plus-maze, whereas the inactive enantiomer d-arginine (100 mg/kg) did not. Neither diazepam alone nor in combination with l- or d-arginine affected the exploratory activity of animals in the open field. Pretreatment with l-arginine (100 and 200 mg/kg) did not modify the motor impairment of rats after diazepam (3 mg/kg) in the rotarod test. Diazepam (2 mg/kg i.p.) did not inhibit the cortical or hippocampal cytosolic NO synthase activity measured ex vivo by [3H]l-arginine assay. Diazepam was similarly ineffective in in vitro studies at concentrations up to 10 μM. We conclude that a suppression of NO synthase activity may be important in the anxiolytic-like effect of benzodiazepines. However, diazepam does not inhibit NO synthase directly, but may affect NO synthase activity indirectly via some unknown mechanism.

Item Type: Journal Article
Publisher: Elsevier
Copyright: © 1998 Elsevier Science B.V.
URI: http://researchrepository.murdoch.edu.au/id/eprint/53007
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