title: Corticotropin-releasing factor (CRF) over-expression down-regulates hippocampal dopamine receptor protein expression and CREB activation in mice.
abstract: BACKGROUND
  Stress results in hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by increased central CRF activity, elevated circulating glucocorticoid levels, impaired glucocorticoid-mediated negative feedback and abnormal hippocampal functions, possibly contributing to the development of behavioral pathologies, such as depression. The hippocampus is critically involved in the control of the HPA axis as well as in explicit memory, contextual aspects of fear, organization of the behavioral response to environmental novelty and in habituation. We have previously shown that mice that over-express CRF in the brain exhibit impaired novelty detection and altered psychophysiological and behavioral habituation, functions linked to dopamine receptor-dependent hippocampal plasticity.
  
  
  OBJECTIVE
  Therefore, the aim of the present study was to measure D1 and D2 dopamine receptor expression and related signaling, such as CREB and ERK protein levels and phosphorylation, in the hippocampus and other brain regions of mice with post-natal CRF over-expression (CRF-OE mice).
  
  
  RESULTS
  We found a region-specific down-regulation of both D1 and D2 protein expression, without altered CRF receptor protein expression, in the hippocampus in CRF-OE mice. This was accompanied by an impaired phosphorylation of hippocampal CREB, but not ERK1 and ERK2, in the same animals.
  
  
  CONCLUSIONS
  These results suggest that post-natal onset CRF over-expression results in an impairment of dopamine signaling in the hippocampus, which may underlie cognitive and motivational aspects of stress-related, CRF-driven mood disorders.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
authors.forename: Maki
authors.initials: M
authors.lastname: Kasahara
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Sarnyai
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000502:physiology; D011954:Receptors, Dopamine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D011954:Receptors, Dopamine; D003346:Corticotropin-Releasing Hormone; D048049:Extracellular Signal-Regulated MAP Kinases