Learning in a 14-unit T-maze is impaired in rats following systemic treatment with N omega-nitro-L-arginine.
We examined whether inhibition of nitric oxide synthase (NO synthase) impairs learning in male Fischer-344 rats (9 mo) in a shock-motivated 14-unit T-maze. Rats were pretrained in one-way active avoidance of foot shock to a criterion of 13/15 avoidances in a straight runway. The next day, rats received intraperitoneal (i.p.) injections of 0.9% NaCl as controls or Nomega-nitro-L-arginine (N-Arg: 3.0. 4.5, or 6.0 mg/kg) to inhibit NO synthase 30 min before maze training. During 15 trials, rats were required to negotiate each of 5 segments within 10 s to avoid footshock. Performance variables included errors (deviations from the correct pathway), runtime from start to goal, shock frequency and duration. N-Arg treatment impaired performance on all variables in a dose-dependent manner. Specifically, only the 6 mg/kg N-Arg dose significantly increased errors compared to controls over the last 10 trials but not the first 5 trials. Controls and rats treated with 3 or 4.5 mg/kg N-Arg were retested in the maze 7-10 days following training, with half receiving N-Arg (6 mg/kg i.p.) 30 min in advance. In this retention test, maze performance was not significantly affected; thus, these results indicated that NO synthase inhibition primarily impaired acquisition without impacting upon noncognitive aspects of performance. This conclusion was further reinforced by the demonstration that 6 mg/kg N-Arg did not significantly affect sensorimotor performance in a rotarod task. When rats were treated with sodium nitroprusside, an NO donor, at 1 min, but not 30 min, prior to training, the N-Arg induced impairment (6 or 8 mg/kg i.p.) in maze learning was significantly attenuated.
Ingram
D K
DK
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Spangler
E L
EL
Meyer
R C
RC
London
E D
ED
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012153:Retention, Psychology / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D019001:Nitric Oxide Synthase