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

Rafael T. Han, Young Beom Kim, Eui Ho Park, Jin Yong Kim, Changhyeon Ryu, Hye Y. Kim, Jae Hee Lee, Kisoo Pahk, Cui Shanyu, Hyun Kim, Seung K. Back, Hee J. Kim, Yang In Kim, Heung Sik Na

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number246
JournalFrontiers in Molecular Neuroscience
Volume11
DOIs
Publication statusPublished - 2018 Aug 14

Fingerprint

Oxytocin
Oxytocin Receptors
Anxiety
Depression
Vasopressin Receptors
Inhibitory Postsynaptic Potentials
Messenger RNA
Neurons
Injections
Paraventricular Hypothalamic Nucleus
Depressive Disorder
Amygdala
Anxiety Disorders
Vasopressins
Constriction
Synaptic Transmission
Hypothalamus
Sucrose
Real-Time Polymerase Chain Reaction
Down-Regulation

Keywords

  • Central amygdala (CeA)
  • Depression and anxiety disorders
  • Gamma-aminobutyric acid
  • Inhibitory synaptic transmission
  • Isolation
  • Oxytocin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala. / Han, Rafael T.; Kim, Young Beom; Park, Eui Ho; Kim, Jin Yong; Ryu, Changhyeon; Kim, Hye Y.; Lee, Jae Hee; Pahk, Kisoo; Shanyu, Cui; Kim, Hyun; Back, Seung K.; Kim, Hee J.; Kim, Yang In; Na, Heung Sik.

In: Frontiers in Molecular Neuroscience, Vol. 11, 246, 14.08.2018.

Research output: Contribution to journalArticle

Han, Rafael T. ; Kim, Young Beom ; Park, Eui Ho ; Kim, Jin Yong ; Ryu, Changhyeon ; Kim, Hye Y. ; Lee, Jae Hee ; Pahk, Kisoo ; Shanyu, Cui ; Kim, Hyun ; Back, Seung K. ; Kim, Hee J. ; Kim, Yang In ; Na, Heung Sik. / Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala. In: Frontiers in Molecular Neuroscience. 2018 ; Vol. 11.
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AU - Lee, Jae Hee

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AU - Shanyu, Cui

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