title: Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood.
abstract: BACKGROUND
  Adverse events during early developmental stages can induce persistent changes in central stress circuits, leading to increased stress sensitivity in adulthood, as is apparent in the maternally separated (MS) rat model. It is widely accepted that the stress peptide corticotropin-releasing factor (CRF) by binding to CRF1 and 2 receptors (CRFR1 and CRFR2) is key to these phenotypic changes.
  
  
  OBJECTIVE
  These studies aim to investigate the effects of maternal separation on central expression of CRFR1 and CRFR2 under basal conditions and following an acute psychological stressor in adulthood.
  
  
  METHODS
  Western blotting techniques were employed to examine changes in receptor expression in the hypothalamus, pre-frontal and frontal cortices, amygdala and hippocampus of MS rats as compared to controls. Additionally, the effects of an acute psychological stressor (open field exposure) on these changes were assessed.
  
  
  RESULTS
  Under basal conditions, CRFR1 was elevated in the hypothalamus of MS rats. Exposure to an acute stress had limited effects in non-separated animals but induced significant changes in CRFR1 in the hypothalamus, pre-frontal cortex and hippocampus of MS rats. Additionally, stress-induced increases in CRFR2 were observed in the amygdala of MS rats.
  
  
  CONCLUSIONS
  These data demonstrate the discrete and significant alterations in how the brain CRF system responds to acute stress following maternal separation. These studies illustrate that early life perturbations induce persistent changes in central CRF receptor expression and increased sensitivity to stress, which may contribute to the stress-related behavioural changes observed in these animals.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Dervla
authors.initials: D
authors.lastname: O'Malley
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008426:Maternal Deprivation; D017397:Prefrontal Cortex / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications*; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone