We have read and appreciate Dr. Mazarati's comments related to our recent review on issues related to preclinical studies of epilepsy comorbidities (Brooks-Kayal et al. Issues related to symptomatic and disease modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy. Epilepsia 2013;54(Suppl. 4):44–60). Dr. Mazarati points out that the tests for depressive-like behavior are not as well validated as those for anxiety-like behavior, particularly in the context of epilepsy models. We agree with his comments that if you are looking for a “true” depression phenotype, there may not be a need to elicit depressive-like behavior with a forced swim session before the forced swim test. However, we would like to note that this approach is useful because it provides an opportunity to collect data from two forced swim sessions, which can be valuable. It may give greater insight into the behavioral phenotype. It would then be important for investigator(s) to carefully consider all of the data and report whether there were effects that could be interpreted as a “basal” change in behavior or a difference (from controls) only during the task. Our overall impression is that several types of analysis for any given behavioral test can often be very helpful and provide in depth information that can be analyzed and reported. Another example of such an analysis would be analyzing and comparing both the first 3 min as well as the first 5 min in Object Recognition and Object Placement testing.
We further agree that Dr. Mazarati's suggestion to include the dexamethasone/corticotropin-releasing hormone test (DEX/CRH) test is valuable and appropriate. Because all behavioral tests have their limitations, utilizing more than one test to demonstrate a consistent phenotype is the optimal approach.