Dexmedetomidine pre-injection attenuates fear response via prelimbic cortex modulation in an electric shock-induced PTSD adolescent rat model.

Abstract

This study compares the pre-injection (48 h before shock) and post-injection (immediately after shock) effects of dexmedetomidine (Dexm) on fear-related behavioral attenuation and brain activity modulation in a post-traumatic stress disorder (PTSD)-like model based on contextual fear conditioning using adolescent Sprague-Dawley rats. Animals were randomly assigned to experimental groups and received intraperitoneal Dexm injections at 20 or 40 μg/kg. Freezing duration, black room preference, black room step-through latency, and black room entry count were measured using the passive avoidance (PA) test. The pre-injection group exhibited dose-dependent reductions in freezing duration and improvements in PA behaviors, particularly at 40 μg/kg, whereas the post-injection group showed no significant Dexm-induced alterations in freezing duration and PA behaviors. Analysis of brain activity changes via c-Fos immunostaining revealed markedly increased activity following Dexm pre-injection only in the mPFC prelimbic region. These results demonstrate that Dexm pre-injection attenuates the electric shock-induced fear response and that this effect is closely linked to increased prelimbic activity in the mPFC. Therefore, this study provides exploratory, preclinical evidence suggesting that Dexm administration prior to fear-inducing experiences may offer pre-stress associative modulation against PTSD-like behavioral development. These findings provide a basis for future research on α-adrenoceptor-mediated PTSD mechanisms.