title: Memory impairment in rats by hippocampal administration of the serine protease subtilisin.
abstract: Since the serine protease subtilisin has been reported to generate a novel form of long-term depression (LTD) in rat hippocampal slices, the present work was designed to determine whether it has any effect on learning and memory processes. Rats were used to examine the effects of subtilisin, injected directly into the dorsal hippocampus, on task performance in a step-through inhibitory avoidance of a mild footshock. The administration of 100 ng of subtilisin into each hippocampus, immediately after training, was sufficient to induce a detectable learning deficit with a footshock stimulus of 0.5 mA. Higher doses produced dose-related impairments in memory consolidation. These effects were not the result of irreversible toxicity, since rats trained with a higher amplitude footshock (0.75 mA) were able to perform as control animals; therefore, the amnesic effect was not further evident. Furthermore, the administration of subtilisin before avoidance training did not produce any detectable effect on performance during the training or test sessions, indicating that neither acquisition nor consolidation was affected. It is concluded that the post-training administration of a serine protease inhibitor is able to produce robust deficits of memory consolidation consistent with its ability to generate LTD, raising the possibility that related molecules could play physiological or pathological roles in the modulation of learning and memory.
authors.affiliation: Instituto de Biología Celular & Neurociencias Prof Eduardo De Robertis, Facultad de Medicina, University of Buenos Aires and CONICET, Buenos Aires, Argentina.
authors.forename: Edgar
authors.initials: E
authors.lastname: Kornisiuk
authors.forename: Marina
authors.initials: M
authors.lastname: Snitcofsky
authors.forename: Carlos
authors.initials: C
authors.lastname: Blanco
authors.forename: Alan L
authors.initials: AL
authors.lastname: Harvey
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Stone
authors.forename: Diana
authors.initials: D
authors.lastname: Jerusalinsky
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology*; D007267:Injections; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D020860:Subtilisin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D015842:Serine Proteinase Inhibitors; D020860:Subtilisin