Oxytocin in dorsal hippocampus facilitates auditory fear memory extinction in rats. (1st January 2022)

• Record Type: Journal Article
• Authors: Bazaz, Amir; Ghanbari, Ali; Vafaei, Abbas Ali; Khaleghian, Ali; Rashidy-Pour, Ali
• Is Part Of: Neuropharmacology. Volume 202(2022)
• Publication Date: 2022-01-01
• Subjects: Oxytocin -- Auditory fear conditioning -- Hippocampus -- Prefrontal cortex -- Infralimbic -- Brain-derived neurotrophic factor; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108844
• Languages: English
• ISSNs: 0028-3908

Abstract

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. This article is part of the special Issue on 'Stress, Addiction and Plasticity'. Highlights: The release of hippocampal (HPC) oxytocin (OT) enhanced during fear extinction. OT injected into dorsal HPC enhanced fear extinction and BDNF the infralimbic (IL). BDNF antagonist ANA-12 injected into the IL blocked the OT effects. OT injected into dorsal HPC enhanced neural activity in the CA1-ventral hippocampus and IL. Activation of the HPC-IL pathway may mediate the enhancing effects of OT on fear extinction.