Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle reflex
Journal
The Journal of neuroscience
Journal Volume
12
Journal Issue
6
Pages
2303-2312
Date Issued
1992
Author(s)
Abstract
Intracerebroventricular infusion of corticotropin-releasing factor (CRF) (0.1-1.0 μg) produced a pronounced, dose-dependent enhancement of the acoustic startle reflex in rats. This excitatory effect began about 20-30 min after infusion, grew steadily over the 2 hr test period, and lasted at least 6 hr. Higher doses of CRF (10 μg) often produced marked facilitation and then inhibition of startle that oscillated repeatedly with a period of 10-20 min. CRF-enhanced startle did not result from an increase in sensitization produced by repetition of the startle stimulus or from a blockade of habituation. Peripheral injections of the autonomic ganglionic blockers hexamethonium (10 mg/kg) or chlorisondamine (3 mg/kg) slightly attenuated the magnitude of CRF-enhanced startle, suggesting a partial role of peripheral sympathetic activation. Intracerebroventricular infusion of the CRF antagonist α-helical CRF9-41 (αhCRF; 25 or 50 μg) blocked CRF-enhanced startle when infused 5 min prior to CRF, indicating a central site of action. CRF-enhanced startle also was reversed when αhCRF was given 90 min after infusion of CRF. This suggests that exogenously applied CRF remains in the brain for a very long time after administration or that CRF given exogenously initiates a process that results in a long-lasting activation of endogenous CRF. Because the startle reflex is elevated by both conditioned and unconditioned fear, these data lend further support to the idea that CRF infusion produces a behavioral state that resembles fear or anxiety. Because startle is mediated by a well-defined neural pathway, CRF-enhanced startle may provide a useful behavioral assay to analyze the neural systems upon which exogenous CRF acts to produce its behavioral effects.
Subjects
chlorisondamine; corticotropin releasing factor; corticotropin releasing factor[9-41]; hexamethonium; animal experiment; animal tissue; anxiety; article; auditory stimulation; autonomic ganglion; behavior; controlled study; dose response; drug effect; facilitation; fear; hypothalamus; hypothalamus hypophysis system; intracerebroventricular drug administration; male; nonhuman; priority journal; protein analysis; protein determination; rat; startle reflex
SDGs
Type
journal article