Reduced startle reactivity and plasticity in transgenic mice overexpressing corticotropin-releasing hormone.
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.
Dirks
Anneloes
A
Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
Groenink
Lucianne
L
Schipholt
Marlies Iutje
MI
van der Gugten
Jan
J
Hijzen
Theo H
TH
Geyer
Mark A
MA
Olivier
Berend
B
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*
D003346:Corticotropin-Releasing Hormone