At present, the research of psychiatric pharmacological treatments in animal models mainly utilizes the comparison of group averages in order to investigate treatment efficacy. Clinically, these treatments usually result in partial success rates. Specifically, the first line pharmacological treatments in PTSD patients are serotonin reuptake inhibitors (SSRIs) and then tricyclic antidepressant (TCAs). Both pharmacological treatments lead to full recovery in less than 30% of PTSD patients, whereas when considering sex differences, men are about as twice more responsive to TCAs than SSRIs. To this day there is a profound lack of knowledge regarding the neural mechanisms that underlie recovery by these pharmacological agents.
We applied a behavioural profiling analysis in an animal model of PTSD with male rats. We differentiated between trauma-affected individuals and unaffected individuals, thereafter treated trauma affected individuals for one month with either SSRIs or TCAs. We than differentiated between the treatment responders and the non-responders based on their behavioural profiling post treatment. Further, we conducted local field electrophysiological recordings from the dorsal dentate gyrus to examine changes in local circuits activity and long-term potentiation (LTP).
Our results revealed responsiveness rates of about 35% to the SSRIs treatment and 60% to the TCAs treatment, alike statistical data from men with PTSD. Further, the electrophysiological recordings revealed significant differences in local circuits and LTP between the responders and non-responders to the SSRIs treatment, but not between responders and non-responders to the TCAs treatment. These findings suggest that a shift in excitatory-inhibitory balance in the hippocampus is likely associated with responsiveness to SSRIs, but not to TCAs. Together, our results suggest a proof of concept for the strong translational power of our behavioural profiling approach for investigating psychiatric pharmacological treatment efficacy.