Involvement of l-arginine-nitric oxide pathway in anxiolytic-like effects of zinc chloride in rats

PurposeZinc is crucial for normal development of the brain, and Zinc deficiency has been shown to associate with neurological disorders (e.g. anxiety) through interactions with several neurotransmitter systems such as nitric oxide (NO). In this regard, our study aimed to evaluate the possible involvement of l-arginine NO pathway on anxiolytic effects of zinc in adult male rats.MethodsZinc chloride at doses of 2.5 and 10 mg/kg (intraperitoneal or ip) or saline (1 ml/kg, ip) were injected 30 min before the anxiety test. Zinc administrated rats (10 mg/kg) were pre-treated with intra-CA1 microinjection of l-arginine in sub-effective dose of 1 μg/rat (dorsal hippocampus, vehicle: saline1 μl/rat). In addition, zinc chloride and NG-nitro-l-arginine methyl ester (l-NAME) were intraperitoneally co-administrated in sub-effective doses of 2.5 mg/kg and 80 mg/kg, respectively. The percentage of open arm time (OAT%), percentage of open arm entry (OAE%), as measures of anxiety, and total number of arm entries, as measures of locomotor activity, were recorded.ResultsTreatment with zinc (10 mg/kg) markedly produced an increase in OAT% and OAE% in the Elevated plus maze test (EPM). A decrease of OAT% and OAE% was shown in groups which received zinc (10 mg/kg) and l-arginine (1 μg/rat) concomitantly as compared to the control group. Moreover, an increase of OAE% was revealed in the group exposed to Zinc (2.5 mg/kg) and l-NAME (80 mg/kg) co-administration. Although, Two-way ANOVA showed no significant differences of anxiety indices in rats received drug + zinc chloride in compare to the zinc pretreated with saline group.ConclusionAnxiolytic- like effect of zinc reversed by nitric oxide precursor l-arginine. Additionally, the synergistic effects of l-NAME and ZnCl2 were shown in the EPM. Thus our findings suggest that at least in part the anxiolytic effects of zinc can be mediated through the nitric oxide system.