Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle reflex.
Intracerebroventricular infusion of corticotropin-releasing factor (CRF) (0.1-1.0 micrograms) 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 micrograms) 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 alpha-helical CRF9-41 (alpha hCRF; 25 or 50 micrograms) blocked CRF-enhanced startle when infused 5 min prior to CRF, indicating a central site of action. CRF-enhanced startle also was reversed when alpha hCRF 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.
Ribicoff Research Facilities of the Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, New Haven 06508.
K C
KC
Liang
K R
KR
Melia
M J
MJ
Miserendino
W A
WA
Falls
S
S
Campeau
M
M
Davis
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects*; D013997:Time Factors
D005730:Ganglionic Blockers; C069206:alpha helical corticotropin-releasing hormone; D003346:Corticotropin-Releasing Hormone