Complex Environmental Rearing Enhances Social Salience and Affects Hippocampal Corticotropin Releasing Hormone Receptor Expression in a Sex-Specific Manner

Neuroscience. 2018 Jan 15:369:399-411. doi: 10.1016/j.neuroscience.2017.11.035. Epub 2017 Nov 29.


Methods for understanding the neurocircuitry of ethologically relevant behaviors have advanced substantially; however renovations to standard animal laboratory housing, in the form of enhanced enrichment, have lagged behind. This is despite evidence that environmental enrichment (EE) reduces stress, stereotypy, and promotes healthy species typical behaviors. While many scientists express interest for increased EE as a standard for animal caging systems, there are concerns that its effects on brain, behavior, and cognition are not well characterized. In the present study, male and female Sprague-Dawley rats were housed for six weeks in either EE, Colony Nesting (CN), or Standard Housing (SD) conditions. We show that adolescent exposure to environmental complexity changed the dynamics of social interactions, sensory processing, and underlying basal stress neurocircuitry, in a sex- and enrichment-type-dependent manner. Specifically, EE and CN increased prosocial engagement and the social saliency of male and female rats while the profile of hippocampal Crhr2 expression was affected only in EE males. Hippocampal Crh was associated with anxiety-like behavior in SD males - this did not extend to EE or CN groups, nor to females. Observations such as these are an important consideration for the validity of translational research investigating the neurocircuitry of stress resiliency, and for understanding the mechanisms of psychiatric disorders. Future work must focus on characterizing how individual environmental enhancements (e.g. novelty, social enrichment, physical activity) shape phenotypic differences, how they vary as a function of species, strain and sex, and (if warranted) how to meaningfully implement this knowledge into biomedical research designs.

Keywords: adaptive; corticosterone, serotonin receptor; corticotropin releasing hormone; corticotropin releasing hormone receptor; enrichment; social behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / metabolism
  • Discrimination, Psychological / physiology
  • Female
  • Gene Expression Regulation, Developmental
  • Habituation, Psychophysiologic / physiology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Housing, Animal*
  • Male
  • Motor Activity / physiology
  • Olfactory Perception / physiology
  • Prefrontal Cortex / growth & development
  • Prefrontal Cortex / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Corticotropin-Releasing Hormone / metabolism*
  • Sex Characteristics*
  • Social Behavior*
  • Stress, Psychological / metabolism


  • CRF receptor type 2
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Corticotropin-Releasing Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone