The first-line pharmacological treatments for PTSD patients are serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). However, both treatments achieve full recovery in fewer than 30% of patients, underscoring the variability in responsiveness among individuals. To this day, there is a profound lack of knowledge regarding the neural mechanisms underlying responsiveness to these treatments. In our study, employing a male rat model of PTSD, we utilized individual behavioral profiling (IBP) following comprehensive behavioral assessments to distinguish between trauma-affected and unaffected individuals. IBP enables personalized analysis by comparing an individual's behavior to the typical distribution of control animals. Following initial assessments, affected rats underwent one month of treatment with either SSRIs or TCAs, followed by additional behavioral evaluations and IBP-based differentiation to treatment responders or non-responders. Electrophysiological recordings (ER) and western blot analysis were conducted. Our findings unveiled differential responsiveness rates between treatments, mirroring the statistical rates observed in men with PTSD. ER data disclosed significant differences in local circuit characteristics between responders and non-responders to SSRI treatment. Western blot analysis revealed distinct patterns of GABA and NMDA receptors subunits expressions following both treatments, according to responsiveness. The results, facilitated by IBP-based differentiation of responders and non-responders, suggest a modulation in the excitation-inhibition balance contingent upon treatment responsiveness. Moreover, they underscore differences in the underlying neural mechanisms associated with responsiveness to each treatment. Moving forward, the study includes examining the responsiveness of female rats to both treatments, encompassing behavioral, ER, and molecular analyses while scrutinizing potential sex differences.