CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors

J Psychiatr Res. 2014 Jun:53:1-7. doi: 10.1016/j.jpsychires.2014.02.015. Epub 2014 Feb 28.

Abstract

Stressful life events during childhood and adolescence are important risk factors for the development of psychopathologies later in life. The corticotropin releasing hormone (CRH) and the CRH receptor 1 (CRHR1) have been implicated in the link between early life adversity and adult anxiety and depression, with rodent studies identifying the very early postnatal period as highly susceptible to this programming. Here, we investigated whether stress exposure during the peripubertal period - comprising juvenility and puberty - is effective in inducing long-lasting changes in the expression of CRHR1 and CRHR2 in the hippocampus and amygdala, and whether treating animals with a CRHR1 antagonist following stress exposure could reverse behavioral alterations induced by peripuberty stress. We show that peripuberty stress leads to enhanced expression of the Crhr1, but not Crhr2, gene in the hippocampal CA1 and the central nucleus of the amygdala, in association with social deficits in the social exploration test and increased stress-coping behaviors in the forced swim test. Treatment with the CRHR1 antagonist NBI30775 (10 mg/kg) daily for 1 week (from P43 to P49), immediately following peripuberty stress exposure, prevented the occurrence of those psychopathological behaviors at adulthood. These findings highlight peripuberty as a period of plasticity for the enduring modulation of the CRHR1 system and support a growing body of data implicating the CRHR1 system in the programming effects of early life stress on eventual psychopathology. They also support recent evidence indicating that temporarily tackling CRHR1 during development might represent a therapeutic opportunity to correct behavioral trajectories linking early stress to adult psychopathology.

Keywords: Anxiety-like behavior; Corticotropin releasing hormone; NBI30775; Peripuberty stress; Social behavior; Stress-coping behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / drug effects
  • Adaptation, Psychological / physiology*
  • Age Factors
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Animals, Newborn
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hormone Antagonists / pharmacology
  • Hormone Antagonists / therapeutic use
  • In Vitro Techniques
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / genetics
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Social Behavior Disorders / drug therapy
  • Social Behavior Disorders / etiology*
  • Stress, Psychological / complications*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / genetics*
  • Stress, Psychological / pathology
  • Swimming / psychology

Substances

  • CRF receptor type 2
  • Hormone Antagonists
  • Pyrimidines
  • R 121919
  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1