Could the prior drug exposure during the EPM test have produced lingering pharmacological or neuroadaptive changes in the hippocampus that influenced behavior during the CFC training session 3 days later? Even if the compound itself is cleared, prior receptor blockade might alter synaptic plasticity or neural network states, affecting how animals acquire the fear memory.
Repeated microinjections into the same brain site can sometimes induce local glial activation or changes in receptor sensitivity. Was there any consideration or control for potential effects of the first injection on the response to the second injection?