EFFECTS OF CHRONIC ADMINISTRATION OF ADENOSINE A(1) RECEPTOR AGONIST AND ANTAGONIST ON SPATIAL-LEARNING AND MEMORY

Spatial memory acquisition in Morris water maze was tested in C57BL/6 mice. Animals were injected once daily with different doses of either N-6-cyclopentyladenosine (CPA) or 8-cyclopentyl-1,3-dipropylxanthine ( CPX). Drugs were administered for 9 days either concurrently with wate r maze testing (drugs injected 1 h after each trial), or prior to the entire block of trials. In the latter case, 1 day without injections p receded water maze experiments. Chronic administration of CPA resulted in a significant, dose-dependent reduction of target latencies, rapid development of spatial preference, and the absence of animals unable to perform the task. CPX treated animals did not show significant perf ormance changes, and failed to develop spatial preference. Locomotor d isturbances were not the cause of the observed effects. Our results in dicate that chronic treatment with agents acting at adenosine A(1) rec eptors results in behavioral effects that are significantly different from those observed following their acute administration. Therefore, p articular caution is required in development of adenosine-based strate gies targeted at neurodegenerative or cognitive disorders in which chr onic treatment is advocated.