Involvement of NO/cGMP pathway in toluene-induced locomotor hyperactivity in female rats

Rationale: Nitric oxide (NO) is implicated in the acute locomotor activating effects of some addictive drugs such as amphetamine, caffeine, and PCP, but has not been investigated in the case of toluene. Objectives: This study determined the contribution of the NO-cyclic GMP (cGMP) pathway to locomotor stimulant effects of toluene. Methods: Locomotor activity was measured for 90 min immediately following toluene (500-1,000 mg/kg, IP) or corn oil treatments in Sprague-Dawley female rats. A NO generator, sodium nitroprusside (SNP) (3 and 6 mg/kg), a NO precursor, L-arginine (L-Arg) (250 mg/kg), a NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME) (5-20 mg/kg, IP), and a soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 mg/kg) were injected 5 min before toluene (750 mg/kg, IP) treatment. The combination effects of SNP with L-NAME, L-arginine with L-NAME, SNP with ODQ and L-arginine with ODQ on toluene-induced locomotor hyperactivity were also determined. Results: The locomotor hyperactivity induced by toluene was significantly inhibited by SNP and L-arginine, but enhanced by L-NAME and ODQ. SNP and L-arginine completely reversed the combined effects of L-NAME and toluene to a basal level and abolished the enhancing effects of ODQ. Conclusions: The results suggested that NO/cGMP-dependent mechanism might be involved in toluene-induced locomotor activity in rats.