Environmental enrichment increases cue-dependent freezing and behavioral despair but decreases anxiety-like behavior in rats

Abstract

While post-traumatic stress disorder (PTSD) can develop after exposure to severe traumatic events, data have shown that individuals with high sensation-seeking personality traits are less prone to developing PTSD. The current study used the rodent environmental enrichment preclinical model of sensation-seeking to determine if similar sensation seeking effects in animal models of PTSD-like behaviors were found. The study also attempted to determine whether environmental enrichment altered the effects of midazolam on these PTSD-like behaviors. Male Sprague-Dawley rats were received at postnatal day (PND) 21 and placed into either an enriched (EC), isolated (IC), or social (SC) condition. Beginning on PND 51, the animals underwent 3 fear conditioning trials where a tone was paired with a 2 s 0.7 mA footshock. Twenty-four hours later, rats were given 15-min i.p. pretreatments of 0, 0.5, or 1.5 mg/kg midazolam, before being placed into fear conditioning chambers for a test of expression of conditioned fear response in a novel context. Following fear conditioning, rodents were also tested in the elevated plus maze (EPM) and the forced swim task (FST) following pretreatments of midazolam. Results from fear conditioning indicated IC rats showed a significant decrease in freezing during acquisition compared to EC and SC rats. Also, during expression, IC rats had lower freezing following saline injections and 0.5 mg/kg midazolam but were equal in time freezing to EC and SC rats following 1.5 mg/kg midazolam. In the EPM there were no effects of midazolam and IC rats showed decreased time spent in the open arms compared to EC and SC rats. In FST, IC rats spent less time immobile and more time swimming compared to EC and SC rats. Overall, results suggest that the rodent environmental enrichment model of sensation-seeking seems to parallel the effects of sensation-seeking on likelihood of PTSD symptoms seen in humans.