Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala

Frontiers in Molecular Neuroscience

Hyun Kim¹  Jin Yong Kim¹  Kisoo Pahk²  Seung K. Back³  Hee J. Kim⁴  Changhyeon Ryu⁵  Eui-Ho Park⁶  Cui Shanyu⁶  Rafael T. Han⁶  Young-Beom Kim⁶  Hye Y. Kim⁶  JaeHee Lee⁶  Yang In Kim⁶  Heung S. Na⁶ 

[1] Department of Anatomy, Korea University College of Medicine, Seoul, South Korea;Department of Neuroscience, Korea University College of Medicine, Seoul, South Korea;Department of Pharmaceutics and Biotechnology, College of Medical Engineering, Konyang University, Chungnam, South Korea;Division of Biological Science and Technology, Science and Technology College, Yonsei University, Wonju, South Korea;Neuroscience Research Institute and Department of Physiology, College of Medicine, Seoul National University, Seoul, South Korea;Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine, Seoul, South Korea;

关键词: oxytocin;    inhibitory synaptic transmission;    central amygdala (CeA);    gamma-aminobutyric acid;    isolation;    depression and anxiety disorders;   

DOI  :  10.3389/fnmol.2018.00246

来源: DOAJ

【 摘 要 】

Isolation stress is a major risk factor for neuropsychiatric disorders such as depressive and anxiety disorders. However, the molecular mechanisms underlying isolation-induced neuropsychiatric disorders remain elusive. In the present study, we investigated the subcellular mechanisms by which long-term isolation elicits depression and anxiety-related behaviors in mice. First, we found that long-term isolation induced depression-related behaviors in the forced swimming test (FST) and the sucrose preference test, as well as anxiety-related behaviors in the elevated zero maze test (EZMT) and the open field test. Next, we showed that intracentral amygdala (CeA) injection of oxytocin (OXT), but not intracerebroventricular injection, attenuated isolation-induced depression and anxiety-related behaviors via oxytocin receptor (OXTR), not vasopressin-1a receptor (V1aR), in the FST and EZMT, respectively. Quantitative real-time polymerase chain reaction analysis revealed that after 5 weeks of isolation, mRNA transcription of OXTR in the CeA, but not that of V1aR, significantly decreased, whereas OXT and vasopressin mRNA transcription in the paraventricular nucleus of hypothalamus did not change significantly. Whole-cell patch clamping of acute brain slices demonstrated that the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in CeA neurons, but not their amplitude, was lower in isolated mice than in group-housed mice. Notably, OXT treatment increased the mIPSC frequency in the CeA neurons, but to a lesser extent in the case of isolated mice than in that of group-housed mice via OXTR. Taken together, our findings suggest that long-term isolation down-regulates OXTR mRNA transcription and diminishes OXT-induced inhibitory synaptic transmission in the CeA and may contribute to the development of depression and anxiety-related behaviors in isolated mice through the enhancement of CeA activity.

【 授权许可】

Unknown