Time-of-day dependence of neurological deficits induced by sodium nitroprusside in young mice

Abstract

Sodium nitroprusside (SNP) is widely used in pharmacological studies as a potent vasodilator or a nitric oxide donor. SNP-induced ataxic effects were assessed in mice by the Joulou-Couvoisier test. Swiss albino mice of both genders, 2-8 weeks of age, were acclimated at least for 2 weeks to 12 h light (rest span)/12 h dark (activity span). In 2 and 4 week old mice, maxima of ataxia were found following intraperitoneal administration of a dose ranging from 3 to 3.6 mg.kg-1 SNP at ≈ 1 and 13 HALO (Hours After Light Onset). The sublethal toxicity was statistically dosing-time dependent (χ2 test: P < 0.005). No rhythm was validated in neurotoxicity by cosinor analyses. At the 8th week of post-natal development (PND), SNP-induced ataxia was greatest at ≈ 1 HALO (69% in males vs. 49% in females) and lowest at ≈ 13 HALO (21% in males vs. 11% in females) (χ2 test: P < 0.00001). Cosinor analysis also revealed no statistically significant rhythm in mice injected with 3 or 3.3 mg.kg-1. However, a significant circadian (τ = 24 h) rhythm was detected by adjusted cosinor in 3.6 mg.kg-1-treated mice (P < 0.004). In all studied groups, SNP-induced motor impairment (expressed in %) was lower during the dark than the light phase. Furthermore, there was a non-significant gender-related difference in SNP-induced neuronal toxicity with the males more sensitive than females at every studied PND. The ataxic effects were inversely proportional to the lag time from injection and to the age of animals (with P < 0.05 only between 2 and 8 week old mice). These data indicate that both the administration time and age of the animal significantly affect the neurotoxic effects of SNP.