L-nitroarginine reduces hippocampal mediation of place learning in the rat.

Based on previous results it was hypothesized that the neural substrate of the acquisition of place learning during inhibition of the nitric oxide synthesizing enzyme (NOS) by L-nitroarginine (L-N-ARG) differs from the neural substrate of normal task acquisition by a reduced or abolished participation of the hippocampus. This hypothesis was tested in two independent experiments. In Experiment 1 the behavioral consequences of bilateral transection of the fimbria-fornix--a lesion that abolishes normal hippocampal function--were investigated in animals that had acquired the task after either a vehicle control pretreatment or a 5-day pretreatment period during which near-total inhibition of NOS had been accomplished by L-N-ARG injections. While fimbria-fornix transections significantly impaired task performance in normal animals the rats which had acquired the task during NOS inhibition did not reveal a lesion-associated impairment. In Experiment 2 four groups of rats were studied: two groups initially received bilateral transection of the fimbria-fornix, while the two others were subjected to sham surgery. Subsequently, one of the fimbria-fornix-transected and one of the sham-operated groups received a 10-day period of L-N-ARG injections, while the two remaining groups received saline control injections. During the final 5 days of injections the four groups were subjected to training on the place-learning task. While NOS inhibition clearly impaired task acquisition in the sham-operated animals, L-N-ARG administration in fimbria-fornix-transected animals failed to impair place-learning acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)