Network neuromodulation of opioid and gabaergic receptors following a combination of “juvenile” and “adult stress” in rats

Omer Horovitz, Ziv Ardi, Shiri Karni Ashkenazi, Gilad Ritov, Rachel Anunu, Gal Richter-Levin

Research output: Contribution to journalArticlepeer-review

Abstract

Early life stress is suggested to alter behavioral responses during stressful challenges in adulthood and to exacerbate pathological symptoms that reminisce posttraumatic stress disorder (PTSD). These effects are often associated with changes in γ-Aminobutyric acid type A (GABAA) and κ opioid receptor expression and neuromodulation of the limbic system. Anxiety-like and stress coping behaviors were assessed in rats exposed to stress in adulthood on the background of previous exposure to stress in juvenility. Two weeks following behavioral assessment in adulthood, GABAAR α1 and α2 subunits and κ opioid receptor expression levels were measured in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, and periaqueductal gray (PAG). To illustrate changes at the network level, an integrated expression profile was constructed. We found that exposure to juvenile stress affected rats’ behavior during adult stress. The combination of juvenile and adult stress significantly affected rats’ long term anxious-like behavior. Probabilities predicting model integrating the expression of GABAA α1-α2 and κ opioid receptors in different brain regions yielded highly successful classification rates. This study emphasizes the ability of exposure to stress in juvenility to exacerbate the impact of coping with stress in adulthood. Moreover, the use of integrated receptor expression network profiling was found to effectively characterize the discussed affective styles and their behavioral manifestations.

Original languageEnglish
Article number5422
Pages (from-to)1-17
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume21
Issue number15
DOIs
StatePublished - 1 Aug 2020

Bibliographical note

Funding Information:
Funding: This research was funded by the Israel Science Foundation (grant No. 1517/16) to G.R.L. and a Ministry of Science, Technology, and Space, State of Israel (MOST) award No. 3-14356 to G.R.L.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Animal models
  • GABA
  • Juvenile stress
  • Neuromodulation
  • Opioid
  • PTSD

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Network neuromodulation of opioid and gabaergic receptors following a combination of “juvenile” and “adult stress” in rats'. Together they form a unique fingerprint.

Cite this