Sustained Separation of Rats into Stress‐Susceptible and Stress‐Resilient Groups by Repeated Exposure to Inescapable Unpredictable Stress

The objective of this study was to create a model in rats wherein learned helpless (LH‐stress‐susceptible) and non‐helpless (NH‐stress‐resilient) behavior were sustained for at least 2 wk after the last inescapable unpredictable tail shock stress (TSS). We hypothesized this could be achieved by repeated bouts of TSS at 3 day intervals, the duration of LH observed after a single TSS session. Rats were subjected to TSS on days 1, 4, and 7. Control groups were Naïve Control (NC) and Tested Control (TC, restraint only, No TSS). Escape deficits were tested on days 8 & 22. Open field test (OFT), elevated plus maze (EPM), and forced swim stress (FSS) tests were done on days 15, 16, and 17 respectively. LH rats (50% of TSS rats) have significantly higher escape latencies/escape failures than NH, TC and NC rats on days 8 & 22 and had significantly higher plasma corticosterone and epinephrine levels (stress markers) on day 22. FSS, but not OFT or EPM, showed significant behavioral changes in LH vs. NH, TC and NC rats. FSS is more stressful than OFT and EPM, suggesting that intensity of stress contributes to behavioral distinction of LH and NH rats. We hypothesize that this model will facilitate understanding of the sustained neurobiological differences that contribute to stress‐susceptible and stress‐resilient groups. (Supported by NARSAD and AHA South‐Central Affilitate)