L-NITROARGININE REDUCES HIPPOCAMPAL MEDIATION OF PLACE LEARNING IN THE RAT

Based on previous results it was hypothesized that the neural substrat e 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 a bolished participation of the hippocampus. This hypothesis was tested in two independent experiments. In Experiment 1 the behavioral consequ ences of bilateral transection of the fimbria-fornix-a lesion that abo lishes normal hippocampal function-were investigated in animals that h ad acquired the task after either a vehicle control pretreatment or a 5-day pretreatment period during which near-total inhibition of NOS ha d been accomplished by L-N-ARG injections. While fimbria-fornix transe ctions significantly impaired task performance in normal animals the r ats which had acquired the task during NOS inhibition did not reveal a lesion-associated impairment. In Experiment 2 four groups of rats wer e studied: two groups initially received bilateral transection of the fimbria-fornix, while the two others were subjected to sham surgery. S ubsequently, 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 th e final 5 days of injections the four groups were subjected to trainin g on the place-learning task. While NOS inhibition clearly impaired ta sk acquisition in the sham-operated animals, L-N-ARG administration in fimbria-fornix-transected animals failed to impair place-learning acq uisition. It is concluded that: (I) Place-learning acquisition in norm al animals involves hippocampus-associated mechanisms that depend on t he integrity of NOS and (II) Under circumstances of NOS inhibition the place-learning task can be acquired by a neural system that differs f rom the system mediating task acquisition in normal animals by receivi ng reduced or absent contributions from the hippocampus. (C) 1995 Acad emic Press, Inc.