DETERMINANTS OF NONSPATIAL WORKING-MEMORY DEFICITS IN RATS GIVEN INTRAVENTRICULAR INFUSIONS OF THE NMDA ANTAGONIST AP5

Two series of experiments using rats assessed the effects of intravent ricular administration of the NMDA antagonist AP5 on performance of no n-spatial working memory tasks. The first series used a continuous del ayed non-matching to sample (DNMS) design; the second series used a di screte trial delayed matching to sample (DMS) design. Performance was assessed at retention intervals ranging from approximately 5 to 90 sec . The subjects had acquired the behavioural tasks before drug testing commenced. In the DNMS series, minipumps containing vehicle, 5, 10 or 15 mM D-AP5 were implanted. Every 10 days, each rat's minipump was rem oved and replaced with a fresh pump containing a new drug dose in a co unterbalanced design, so that all rats were tested under all four cond itions. There were no drug effects on performance at any retention int erval. In the DMS series, there were three different basic task varian ts. Minipumps filled either with 15 mM D-AP5 or vehicle solution were implanted. Vehicle rats performed at approximately pre-operative level s; AP5 rats were impaired only on task variants using repeated stimulu s presentations within session. There was no interaction between reten tion interval and drug treatment. This pattern of results closely rese mbles that seen following hippocampectomy or fornicotomy, as would be expected if this drug, administered intraventricularly, selectively af fected hippocampal function.