Predator odor evokes sex-independent stress responses in male and female Wistar rats and reduces phosphorylation of cyclic-adenosine monophosphate response element binding protein in the male, but not the female hippocampus.

Abstract

Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling cascades in the male and female hippocampus which may contribute to behavioral disruptions associated with predator exposure.