The Single-Prolonged Stress Model Fails to Produce Behavioral or Corticosterone Alterations in Rats

There is a critical need for robust and reliable preclinical models for posttraumatic stress disorder (PTSD) to better understand pathophysiological mechanisms and support the development of novel treatments. The single prolonged stress (SPS) model has been previously utilized to investigate various acute behavioral effects and stress hormone changes in rodents. This study paired anxiety-like and social behavioral evaluations with corticosterone assessment as a complementary physiological biomarker to determine the presence of robust and intervenable phenotypes following SPS. Sprague Dawley rats (<i>N</i> = 36, 30 male and 6 female) received SPS model induction (e.g., restraint with odorant, forced-swim, diethyl ether exposure, and isolation) or control handling. Serum corticosterone and behavioral assessments, including the open field test (OFT) and a social motivation test (SMT), were investigated at 1 and 2 weeks following SPS induction. This SPS model did not induce anxiety-like or locomotive differences assessed in the OFT (<i>p</i>'s > 0.05). Similarly, SPS did not appear to alter social preference or avoidance in the SMT (<i>p</i>'s > 0.05), as groups had similar novel social and novel object interaction levels. SPS-paired cue re-exposure did not unmask group differences in these behaviors. Corticosterone levels were also unaltered between groups in the weeks following SPS (<i>p</i> = 0.178). In the absence of other stressors or modifications, the null behavioral and corticosterone findings in the weeks following SPS suggest that this SPS protocol may not reliably produce adequately robust or intervenable phenotypes.