AI Article Synopsis
- Fear extinction is crucial for treating psychiatric disorders, and oxytocin (OT) has been identified as a potential facilitator in this process.
- The study found that endogenous OT levels significantly increase during fear extinction in the dorsal hippocampus (dHPC), suggesting it enhances the fear extinction process, especially when combined with BDNF.
- OT's effects involve increased neural activity in critical brain regions, like the CA1-vHPC and the infralimbic cortex, underscoring the importance of the dHPC-mPFC pathway in fear extinction mechanisms.
Article Abstract
Fear extinction is impaired in some psychiatric disorders. Any treatment that facilitates the extinction of fear is a way to advance the treatment of related psychiatric disorders. Recent studies have highlighted the role of oxytocin (OT) in fear extinction, but the endogenous release of OT during fear extinction in the dorsal hippocampal (dHPC) is not clear. We investigated the release of OT during fear extinction and the role of the HPC - medial prefrontal cortex (mPFC) circuit and BDNF in the effects of exogenous OT on auditory fear conditioning in male rats. We found that the release of endogenous OT in the dHPC is significantly increased during the fear extinction process as measured by the microdialysis method. Increased freezing response in the OT-treated rats compared to saline-treated rats showed that exogenous OT in the dHPC enhanced the fear extinction. Injection of BDNF antagonist (ANA-12) into the infralimbic (IL) blocked the effect of exogenous OT on the dHPC. Following OT injection, BDNF levels increased in the dHPC, ventral HPC, and IL cortex; but decreased in the prelimbic cortex (PL). Finally, OT microinjected into the dHPC significantly increased neural activity of pyramidal neurons of the CA1-vHPC and IL but decreased the neural activity in the PL cortex. Our findings strongly support that the dHPC endogenous OT plays a crucial role in enhancing fear extinction. It seems that the activation of the HPC-mPFC pathway, and consequently, the release of BDNF in the IL cortex mediates the enhancing effects of OT on fear extinction.
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| http://dx.doi.org/10.1016/j.neuropharm.2021.108844 | DOI Listing |
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