L-Arginine abolishes the anxiolytic-like effect of diazepam in the elevated plus-maze test in rats.
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 microM. 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.
Department of Physiology, University of Tartu, Estonia. vallov@ut.ee
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D058785:GABA-A Receptor Agonists; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D003975:Diazepam