Intra-CA۱ administration of FK-۵۰۶ (tacrolimus) in rat impairs learning and memory in an inhibitory avoidance paradigm

Objective(s): Calcineurin (CN) is a main phosphatase and a critical regulator of cellular pathways for learning, memory, and plasticity. The FK-۵۰۶ (tacrolimus),a phosphatase inhibitor, is a fungal-derived agent and a common immune suppressant extensively used for tissue transplantation. To further clarify the role of CN in different stages oflearning and memory the main aim of this study was to evaluate the role of FK-۵۰۶ in an inhibitory avoidance model. Materials and Methods:Using different doses of FK-۵۰۶ (۰.۵, ۵, and ۵۰ nM) in the CA۱ of hippocampus at different times (before, after the training and also before the test), the effect of drug was evaluated in a step-through inhibitory avoidance paradigm.The latency of entering to the dark compartment was considered as a criterion for memory. Results:  Thepre-training intra-CA۱ injections of FK-۵۰۶ impaired inhibitory avoidance (IA) learning acquisition. In addition, thepost-training intra-CA۱ injections of FK-۵۰۶ at ۱, ۲, and ۳ hr relative to training impaired memory consolidation. Moreover, thepre-test intra-CA۱ injections of FK-۵۰۶ impaired memory retrieval. Conclusion:These findings suggest that the FK-۵۰۶ selectively interferes with acquisition, retention, and retrieval of information processing in CA۱ of hippocampus. Given the crucial role of CN in common signaling pathway of higher functions such as memory performance and cognition, in future it would be a probable therapeutic target in the treatment of a wide verity of neurological conditions involving memory.

Keywords:

Avoidance learning , Calcineurin , FK-۵۰۶ , Learning , Memory , Phosphatase inhibitor , Rat , Tacrimolus