Nitric oxide synthetase inhibition hinders facilitation of active avoidance learning by nicotine in rats

Nicotine produces dose-dependent enhancement of performance in an active av oidance test, and also increases the levels of NO2- and NO3-, which are sta ble metabolites of nitric oxide (NO), in various brain regions of rats. On the basis of these two observations, we hypothesized that the beneficial ef fect of nicotine on learning could result from increased NO in relevant bra in regions. We therefore tested active avoidance performance in rats given L-N-omega-nitroarginine (L-NA) to inhibit NO synthetase (NOS) prior to nico tine administration, Male Sprague-Dawley rats received L-NA (30 or 50 mg/kg ), nicotine (0.4 mg/kg), saline or combinations of these treatments before learning trials. Rats were also tested on the inclined plane, to assess the possible effects due to impairment of motor function by drug treatments on active avoidance learning. L-NA treatment impaired the acquisition of acti ve avoidance learning, and this defect was partially overcome by the co-adm inistration of nicotine. Nicotine facilitated learning and significantly in creased the number of correct responses. The threshold for the effect of NO S inhibition on performance exceeded 30 mg/kg L-NA, whereas 50 mg/kg impair ed learning and also eliminated the nicotine-induced enhancement of learnin g. On the fifth day of learning trials, no facilitation of learning by nico tine was observed in rats receiving either dose of L-NA. Our results sugges t that NO is involved in the facilitation of active avoidance learning by n icotine. (C) 2000 Lippincott Williams & Wilkins.