Abstract
The involvement of nitrergic mechanisms in the behavioural effects of withaferin A 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 withaferin A (40 mg/kg, i.p.) in the elevated plus-maze, whereas the inactive enantiomer D-arginine (100 mg/kg) did not. Neither withaferin A 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 withaferin A (40 mg/kg) in the rotarod test. Withaferin A (40 mg/kg i.p.) did inhibit the brain NO synthase activity measured ex vivo by NOx assay. We conclude that a suppression of NO synthase activity may be important in the anxiolytic-like effect of withaferin A. Key words: Withaferin A, nitric oxide (NO) synthase, L-Arginine , anxiety, elevated plus maze test.
Highlights
Nitric oxide (NO) has been recognized as an intercellular messenger in the central nervous system (Bredt and Snyder, 1989)
Withaferin A (40 mg/kg i.p.) caused a significant increase in percen-tage of open arm visits (P
L-Arginine seems to cause a true change in the anxiolytic-like action of withaferin A
Summary
Nitric oxide (NO) has been recognized as an intercellular messenger in the central nervous system (Bredt and Snyder, 1989). Withaferin A share have an anxiolytic-like effect, decrease motor activity, possess an anticonvulsant effect and decrease cyclic GMP content (Khan and Ghosh, 2010; Kulkarni and Dhir, 2008; Bhattacharya, 2002; Bredt and Snyder, 1989). We hypothesized that the brain nitrergic system may be involved in some of the effects of withaferin A. The aim of the present study was to elucidate whether the behavioural effects of an anxiolytic, withaferin A, could be modulated by the NO precursor L-arginine. The effect of withaferin A on the brain NO synthase activity was measured in ex vivo
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