EN
Literature data show the relationship between L-arginine:NO:cGMP pathway and g-aminobutyric acid (GABA)-mediated transmission in the central nervous system. Benzodiazepines are known to enhance the GABA-ergic neurotransmission and well established as inhibitory modulators of memory processing. More-over, the role of NO in learning and memory processes has been proposed. The present studies were designed to evaluate the role of L-arginine:NO:cGMP pathway in the amnesic effects of diazepam (DZ) in the modifi ed elevated plus-maze (mEPM) task in mice. Our experiments indicated that DZ (1 mg/kg, s.c.) impaired elevated plus-maze memory performance in mice. Pretreatment with L-arginine, the NO precursor, (500 mg/kg, i.p.) prevented the amnesic properties of DZ. While, 7-nitroindazole (7-NI), the neuronal NO synthase inhibitor (nNOS), (40 mg/kg, i.p.) and methylene blue (MB), the soluble guanylate cyclase (sGC) inhibitor, (5 mg/kg, i.p.) enhanced the DZ-induced memory defi cits. Moreover, the effect of both 7-NI and MB were reversed by L-arginine (250 mg/kg, i.p.). It is important to note that presented data are not due to either 7-NI-, MB-induced impairment of memory or changes in locomotor activity, because 7-NI and MB given alone, had no impact on the mEPM behaviour and locomotor activity of mice. Taken together, these results suggest that an inhibition of the Larginine:NO:cGMP pathway may be involved in the amnesic effects of benzodiazepines.