title: L-nitroarginine reduces hippocampal mediation of place learning in the rat.
abstract: 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)
authors.affiliation: Department of Pharmacology, University of Copenhagen, University Hospital, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Mogensen
authors.forename: G
authors.initials: G
authors.lastname: Wörtwein
authors.forename: B
authors.initials: B
authors.lastname: Gustafson
authors.forename: P
authors.initials: P
authors.lastname: Ermens
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase