Inhibition of nitric oxide synthase reduces ultrasonic vocalizations of rat pups

The present study investigated the effects of drugs acting on the brain nitric oxide pathway on ultrasonic vocalizations, body temperature and locomotion in 7-8-day-old rat pups. Both a selective neuronal nitric oxide synthase (NOS) inhibitor (7-nitroindazole) and a non-selective NOS inhibitor (nitro-L-arginine-methyl ester, L-NAME) decreased the number of ultrasonic vocalizations in a dose-dependent manner. The non-selective NOS inhibitor, L-NAME, suppressed not only ultrasonic vocalizations but also locomotion. The inactive isomer of the NOS inhibitor, nitro-D-arginine-methyl ester (D-NAME), and the biological precursor of nitric oxide, L-arginine, had no effect on ultrasonic vocalizations or locomotion. These data indicate that drugs suppressing nitric oxide synthesis produced an anxiolytic effect in rat pups. However, only the selective NOS inhibitor, 7-nitroindazole, was 'anxioselective', i.e., reduced ultrasonic vocalizations without causing sedation. Increased synthesis of nitric oxide in the brain had no apparent behavioral effect in this model.