Strain Differences Determine the Response to Citalopram on Hippocampal Neurogenesis, Neurotrophin Mobilization and Behavior

Abstract

The objective of this study is to examine strain differences on measures of antidepressant‐related behavior and hippocampal neurogenesis in response to chronic treatment with the selective serotonin reuptake inhibitor citalopram. MRL/MpJ mice, known for superior wound healing and resilience to stress, were compared with C57Bl/6J mice on responses to chronic infusion of the selective serotonin reuptake inhibitor citalopram (5 mg/kg/day for 21 days). The animals were then evaluated in the novelty‐induced hypophagia (NIH) test and examined for increased hippocampal cell proliferation after BrdU labeling by flow cytometry. Exposure to chronic citalopram significantly reduced the latency to approach food in a novel environment in the NIH paradigm in the MRL/MpJ mouse strain but had no effect on approach latency in C57Bl/6J mice. MRL/MpJ mice also showed increased cell proliferation and increased BDNF levels in response to citalopram treatment, while C57Bl/6J mice showed no significant change in cell proliferation or BDNF levels. Overall, MRL/MpJ mice showed a significant behavioral and neurobiological response to citalopram, in contrast to the C57Bl/6J strain. These results indicate that strain differences strongly impact responses to chronic citalopram. Future studies will determine the mechanisms of antidepressant action in these mice.This research was supported by USPHS T32 MH14654 and R01 MH72832.