Intracerebroventricular injection of Nω-nitro- l-arginine in rats impairs learning in a 14-unit T-maze

Abstract

We investigated whether intracerebroventricular (i.c.v.) infusion of the nitric oxide synthase inhibitor, N ω -nitro- l-arginine ( N-Arg), impairs learning in male Sprague–Dawley rats (2–3 months old) in a 14-unit T-maze. Rats were pretrained in one-way active avoidance to a criterion of 13/15 avoidances of foot shock in a straight runway. The next day, rats received i.c.v. injections of either artificial cerebrospinal fluid (aCSF) as controls or N-Arg (12 μg or 15 μg) 30 min before training in the 14-unit T-maze. The learning contingency was to negotiate each of 5 segments within 10 s to avoid footshock during 15 trials. Performance variables included errors (deviations from the correct pathway), runtime from start to goal, and shock frequency and duration. Compared to controls, the number of errors over the last 10 trials was higher in rats receiving 15 μg N-Arg and over the last 5 trials for those given 12 μg. Runtime, shock frequency and duration were increased in both N-Arg groups. The N-Arg-induced (15 μg i.c.v.) impairment could be attenuated when the nitric oxide donor, sodium nitroprusside (1 mg/kg), was administered intraperitoneally 1 min prior to maze learning. In a retention test, rats were treated with either aCSF or 15 μg N-Arg i.c.v. 30 min before being retested in the maze 7–10 d following acquisition training. Under these conditions, maze performance was not significantly affected. These results confirmed previous findings that inhibition of nitric oxide synthase impairs acquisition but not retention. Moreover, the N-Arg-induced learning impairment does not appear to be related to noncognitive aspects of performance.