title: Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain.
abstract: OBJECTIVE
  A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats.
  
  
  METHODS
  Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg(6) Phe(7) (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA.
  
  
  RESULTS
  Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B.
  
  
  CONCLUSIONS
  Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment.
  
  
  BACKGROUND
  This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
authors.affiliation: Department of Pharmaceutical Biosciences, Neuropharmacology, Addiction and Behaviour, Uppsala University, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Granholm
authors.forename: E
authors.initials: E
authors.lastname: Roman
authors.forename: I
authors.initials: I
authors.lastname: Nylander
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004399:Dynorphins / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D006799:Housing, Animal; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012931:Social Environment; D000097629:Nociceptin
chemical_list: D004399:Dynorphins; D004723:Endorphins; D004744:Enkephalin, Methionine; D018847:Opioid Peptides; D000097629:Nociceptin; C027511:enkephalin-Met, Arg(6)-Phe(7)-; C036200:rimorphin
keywords: dynorphin; early stress; enkephalin; nociceptin/orphanin FQ; rats; social environment