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Intra-CA1 administration of FK-506 (tacrolimus) in rat impairs learning and memory in an inhibitory avoidance
Amirmasoud Hadjiasgary1, Hamid Reza Banafshe2, Abolfazl Ardjmand1
1Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Objectives:
Calcineurin (CN) is a main phosphatase and a critical regulator of cellular pathways for learning, memory, and plasticity. The FK-506 (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 of learning and memory the main aim of this study was to evaluate the role of FK-506 in an inhibitory avoidance model.
Materials And Methods:
Using different doses of FK-506 (0.5, 5, and 50 nM) in the CA1 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:
The pre-training intra-CA1 injections of FK-506 impaired inhibitory avoidance (IA) learning acquisition. In addition, the post-training intra-CA1 injections of FK-506 at 1, 2, and 3 hr relative to training impaired memory consolidation. Moreover, the pre-test intra-CA1 injections of FK-506 impaired memory retrieval.
Conclusion:
These findings suggest that the FK-506 selectively interferes with acquisition, retention, and retrieval of information processing in CA1 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.
Insights
FK-506 (tacrolimus) impairs memory acquisition, consolidation, and retrieval in the hippocampus. This phosphatase inhibitor highlights calcineurin
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Calcineurin (CN) is a key phosphatase regulating learning, memory, and neural plasticity.
- FK-506 (tacrolimus), a CN inhibitor, is an immunosuppressant with potential neurological effects.
Purpose of the Study:
- To investigate the role of FK-506 in different memory stages using an inhibitory avoidance model.
- To evaluate FK-506's impact on memory acquisition, consolidation, and retrieval in the hippocampus.
Main Methods:
- Administered varying doses of FK-506 into the CA1 region of the hippocampus.
- Tested FK-506's effects at different time points: before training, after training, and before testing.
- Assessed memory using a step-through inhibitory avoidance paradigm, measuring latency to enter the dark compartment.
Main Results:
- Pre-training FK-506 injections impaired inhibitory avoidance learning acquisition.
- Post-training FK-506 injections impaired memory consolidation at 1, 2, and 3 hours post-training.
- Pre-test FK-506 injections impaired memory retrieval.
Conclusions:
- FK-506 selectively disrupts information processing (acquisition, retention, retrieval) in the hippocampal CA1.
- Calcineurin's role in memory suggests FK-506 could be a therapeutic target for memory-related neurological conditions.

