Nitric oxide synthesis inhibition does not affect brain stimulation reward

The effect of nitric oxide synthesis inhibition on brain stimulation reward was examined. A wide range of doses of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 30-300 mg/kg IP) failed to affect frequency thresholds for brain stimulation reward. The effect of L-NAME on cocaine's facilitation of brain stimulation reward was also examined. Nitric oxide synthesis inhibition had no effect on cocaine's ability to lower reward thresholds for electrical brain stimulation. Despite reports that nitric oxide may modulate dopamine release, these data suggest that nitric oxide is not involved in the dopamine-dependent rewarding effect of electrical brain stimulation or the reward facilitation produced by cocaine's enhancement of dopaminergic activity. Because L-NAME potently decreases cerebral blood flow, its lack of effect on cocaine-enhanced brain stimulation reward has additional significance. The failure of a moderate dose of L-NAME (30 mg/kg IP) to attenuate cocaine's lowering of reward thresholds argues against pharmacokinetic explanations of L-NAME's effect on other cocaine-induced behaviors.