Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain

We investigated the effects of N^G‐nitro‐L‐arginine methyl ester (L‐NAME), an inhibitor of nitric oxide (NO) synthase, on the performance of rats in a radial arm maze and in habituation tasks, and on monoamine metabolism in the brain. Daily administration of L‐NAME (10–60 mg kg⁻¹) resulted in a dose‐dependent impairment of performance during the acquisition of the radial arm maze task, while it failed to affect performance in those rats that had previously acquired the task. The rate of decrease in locomotor activity in the habituation task in the L‐NAME‐treated rats was significantly less than that in control rats. N^G‐nitro‐D‐arginine methyl ester (D‐NAME, a less active inhibitor of NO synthase) showed no effects in the above behavioural tasks. NO synthase activity was significantly decreased in both the L‐NAME and D‐NAME‐treated rats, with the magnitude of inhibition being greater in the L‐NAME‐treated animals. The content of 5‐hydroxyindoleacetic acid (5‐HIAA) in the hippocampus and the 5‐HIAA/5‐hydroxytryptamine ratio in the hippocampus and cortex were significantly decreased in the L‐NAME (60 mg kg)‐treated rats compared with these values in the controls. Striatal 3,4‐dihydroxyphenylacetic acid (DOPAC) content was significantly increased in the L‐NAME (60 mg kg^_1)‐treated rats compared with the values in the controls, while the DOPAC/dopamine ratio was not changed. These results suggest that: (i) NO may play an important role in performance during the acquisition, but not retention, of the radial arm maze task, and (ii) that endogenous NO may be involved in the regulation of monoamine metabolism. 1995 British Pharmacological Society