Moaddab Mahsa, Dabrowska Joanna
Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA; Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Neuropharmacology. 2017 Jul 15;121:130-139. doi: 10.1016/j.neuropharm.2017.04.039. Epub 2017 Apr 26.
Oxytocin (OT) is a hypothalamic neuropeptide that modulates fear and anxiety-like behaviors. Dorsolateral bed nucleus of the stria terminalis (BNST) plays a critical role in the regulation of fear and anxiety, and expresses high levels of OT receptor (OTR). However, the role of OTR neurotransmission within the BNST in mediating these behaviors is unknown. Here, we used adult male Sprague-Dawley rats to investigate the role of OTR neurotransmission in the BNST in the modulation of the acoustic startle response, as well as in the acquisition and consolidation of conditioned fear using fear potentiated startle (FPS) paradigm. Bilateral intra-BNST administration of OT (100 ng) did not affect the acquisition of conditioned fear response. However, intra-BNST administration of specific OTR antagonist (OTA), (d(CH), Tyr(Me), Thr, Orn, des-Gly-NH)-vasotocin, (200 ng), prior to the fear conditioning session, impaired the acquisition of cued fear, without affecting a non-cued fear component of FPS. Neither OTA, nor OT affected baseline startle or shock reactivity during fear conditioning. Therefore, the observed impairment of cued fear after OTA infusion resulted from the specific effect on the formation of cued fear. In contrast to the acquisition, neither OTA nor OT affected the consolidation of FPS, when administered after the completion of fear conditioning session. Taken together, these results reveal the important role of OTR neurotransmission in the BNST in the formation of conditioned fear to a discrete cue. This study also highlights the role of the BNST in learning to discriminate between threatening and safe stimuli.
催产素(OT)是一种下丘脑神经肽,可调节恐惧和焦虑样行为。终纹床核背外侧部(BNST)在恐惧和焦虑调节中起关键作用,并表达高水平的OT受体(OTR)。然而,BNST内OTR神经传递在介导这些行为中的作用尚不清楚。在此,我们使用成年雄性Sprague-Dawley大鼠,通过恐惧增强惊吓(FPS)范式,研究BNST中OTR神经传递在调节听觉惊吓反应以及条件性恐惧的获得和巩固中的作用。双侧向BNST内注射OT(100 ng)不影响条件性恐惧反应的获得。然而,在恐惧条件训练前,向BNST内注射特异性OTR拮抗剂(OTA),即(d(CH),Tyr(Me),Thr,Orn,des-Gly-NH)-血管催产素(200 ng),会损害线索性恐惧的获得,但不影响FPS的非线索性恐惧成分。在恐惧条件训练期间,OTA和OT均不影响基线惊吓或电击反应性。因此,注射OTA后观察到的线索性恐惧受损是由于对线索性恐惧形成的特异性作用。与获得过程不同,在恐惧条件训练完成后注射OTA或OT均不影响FPS的巩固。综上所述,这些结果揭示了BNST中OTR神经传递在对离散线索形成条件性恐惧中的重要作用。本研究还强调了BNST在学习区分威胁性和安全性刺激中的作用。