Effects Following Intracerebroventricular Injection of Immunosuppressant Cyclosporine A On Inhibitory Avoidance Learning and Memory in Mice.

Abstract

Background: Protein phosphatase-2B or calcineurin (CN) is the main phosphatase and a critical regulator of cellular pathways for learning, memory, and plasticity. Cyclosporine A(CyA), a phosphatase and peptidyl-prolyl cis/trans isomerase inhibitor, is a common immune suppressant extensively used in tissue transplantation. To further clarify the role of CN in different stages of learning and memory, the aim of the present study was to evaluate the role of CyA in an inhibitory avoidance (IA) model in mice. Materials and Methods: Using intracerebroventricular (ICV) injection of different doses of CyA (0.5, 5, and 50 nM) at different periods (pre-/post-training and pre-test), the effect of the drug was evaluated in a step-down IA paradigm. The latency of step-down (sec) was considered a criterion for memory performance. Results: The pre-training injections of CyA (0.5, 5 nM), however not of 50 nM, impaired IA learning acquisition. The post-training injection of high-dose CyA (50 nM) impaired memory consolidation. The pre-test ICV CyA injection did not impair memory retrieval; the ICV injection of CyA caused no change in locomotion. Conclusion: These findings suggest that CyA selectively interferes with acquisition, retention, but not retrieval, of information processing in mice. Given the crucial role of CN in common signaling pathway of memory performance and cognition, it could be a probable therapeutic target in the treatment of a wide variety of neurological conditions involving memory.