PS257. The effects of brain-derived neurotrophic factor (BDNF) micro-infusion on the impaired fear extinction of the animal model of PTSD.

Abstract

Although the impaired extinction of fear memory (Ext) is one of the hallmark symptoms of posttraumatic stress disorder (PTSD), the underlying mechanisms of impaired Ext are unclear and effective pharmacological interventions have not yet been developed. Recently, the neuronal plasticity induced by brain-derived neurotrophic factor (BDNF) in infralimbic (IL) prefrontal cortex and/or hippocampus were shown to be crucial for the Ext of naïve rats.

We used a single prolonged stress (SPS) paradigm, which mimic the pathophysiological abnormalities and behavioral characteristics of PTSD including the impaired Ext. The current study was conducted to investigate the expression of BDNF in the brain of SPS rats, as well as the therapeutic efficacy of intracranial BDNF micro-infusion for the impaired Ext of SPS. Either the sacrifice of rats for BDNF quantification or the micro-infusions for the behavioral study were conducted just before Ext training session (24hr after fear conditioning), and the micro-infusions were targeted to the IL, or Prelimbic (PL) prefrontal cortex, or ventral hippocampus (vHPC).

The mature BDNF protein expression of SPS rats were significantly reduced just before Ext training in both the medial prefrontal cortex and the hippocampus. In addition, the micro-infusion of BDNF into IL or into vHPC, but not into PL, induced the significant reduction of freezing behavior at the Ext training session and Ext test session (24hr after Ext training), and these effects were commonly seen in the naïve rats and the SPS rats.

Our results indicates that the neuronal plasticity induced by BDNF in IL and vHPC are, at least in part, involved in the mechanism of the Ext even in the PTSD. At the meeting, we will show the changes in the phosphorylation of TrkB (an receptor of BDNF) after the micro-infusion of BDNF.