The link between learning performance, immobility in the forced swim test, and hippocampal glia

Aim: To obtain maximal translational insights from animal models of depression, we need to know the meaning of behavioral parameters of animal models. The extent of construct and face validities of behavioral despair in the form of behavioral immobility in forced swim test (FST) is disputed. In this study, learning performance in a dual solution T-Maze and immobility on the 2nd day of FST was compared to shed light on this debate. Furthermore, we aimed to inspect the relationship between hippocampal glial densities and behaviors observed. Method: Twelve adult male Sprague Dawley rats were tested in the dual-solution T-Maze and in FST. Subsequently, hippocampal slices were obtained, astrocyte and microglia cells were stained, and the densities were calculated for each subject. Results: The rats utilized different learning strategies to solve the T-Maze. But irrespective of strategy, the rats that exhibited an overall efficiency in their learning performance, remained immobile for longer durations on the 2nd day of the FST. No significant relationship was detected between hippocampal microglia and behavioral indices in T-Maze and FST. However, we detected a significant positive correlation with CA1 astrocyte density and T-Maze learning and dentate gyrus CA1 astrocyte density and headshake behavior in FST. Conclusions: The subjects showing a better cognitive performance in the T-Maze were immobile longer in the FST. This observation raises doubts about immobility as depression index and posits that it might reflect better learning. Our results also suggest that hippocampal glia cell types are differentially involved in cognition and affect