Catalepsy and hypolocomotion induced by a nitric oxide donor: attenuation by theophylline

Abstract

Nitric oxide (NO) promotes adenosine release in the striatum and hippocampus. Behavioral effects of the nitric oxide donor sodium nitroprusside were studied in mice and included an examination of spontaneous locomotion and catalepsy, which are behaviors modulated by adenosine. Sodium nitroprusside caused a dose-dependent (2, 4 and 6 mg/kg) decrease in locomotor activity and catalepsy at the dose of 6 mg/kg. These effects were substantially attenuated by pretreatment with the non-selective adenosine receptors antagonist theophylline (10 and 30 mg/kg). Moreover, combined treatment with theophylline (30 mg/kg) and sodium nitroprusside (6 mg/kg) induced limbic seizures in 23% of animals. The pretreatment with the selective adenosine A 1 receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT) (1.2 mg/kg) caused no effect on the spontaneous or sodium nitroprusside-induced behavior. These data suggest that these behavioral effects of sodium nitroprusside are at least partially mediated by adenosine in the striatum and hippocampus, probably via adenosine A 2A receptors.