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-OE2122) 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-OE2122 mice. Methods: CRH-OE2122 mice (on C57BL/6J background) were subjected to a number of procedures probing sensory, information processing mechanisms, including the acoustic startle response, habituation, and perpulse inhibition of startle. Results: CRH-OE2122 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-OE2122 mice exhibited robust impairments of prepulse inhibition in two different paradigms. Conclusions: The results in CRH-OE2122 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. (C) 2002 Society of Biological Psychiatry.