title: Reduced startle reactivity and plasticity in transgenic mice overexpressing corticotropin-releasing hormone.
abstract: BACKGROUND
  Corticotropin-releasing hormone (CRH) hyperactivity in transgenic mice overexpressing CRH in the brain (CRH-OE(2122)) appears to be associated with chronic stress-like alterations, including increased CRH content in the hypothalamus, changes in hypothalamus-pituitary-adrenal axis regulation, and increased heart rate and body temperature. In the present study, we investigated if sensory information processing of startling auditory stimuli was affected in CRH-OE(2122) mice.
  
  
  METHODS
  CRH-OE(2122) mice (on C57BL/6J background) were subjected to a number of procedures probing sensory information processing mechanisms, including the acoustic startle response, habituation, and prepulse inhibition of startle.
  
  
  RESULTS
  CRH-OE(2122) mice displayed reduced acoustic startle reactivity and increased motor activity during startle testing compared to wild-type mice. Furthermore, transgenic mice did not show habituation of the startle response after repeated exposure to the auditory stimulus, or habituation across procedures. CRH-OE(2122) mice exhibited robust impairments of prepulse inhibition in two different paradigms.
  
  
  CONCLUSIONS
  The results in CRH-OE(2122) mice indicate that chronic CRH hyperactivity is associated with reductions in startle reactivity, habituation, and prepulse inhibition. The latter two abnormalities are also observed in schizophrenia patients. We conclude that chronic CRH excess may reduce behavioral reactivity to environmental stimuli and impair information processing mechanisms.
authors.affiliation: Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
authors.forename: Anneloes
authors.initials: A
authors.lastname: Dirks
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: Marlies Iutje
authors.initials: MI
authors.lastname: Schipholt
authors.forename: Jan
authors.initials: J
authors.lastname: van der Gugten
authors.forename: Theo H
authors.initials: TH
authors.lastname: Hijzen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001143:Arousal / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000502:physiology; D013216:Reflex, Startle / Q000235:genetics*
chemical_list: D003346:Corticotropin-Releasing Hormone