Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle reflex
Open accessAbstract
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.
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After CRF infusion, startle rises from roughly 30 min, increases across a 2-h session, and persists for hours.
“large, dose-dependent increases in startle amplitude that began ∼30 min after CRF infusion, grew steadily over the course of a 2-h test period, and lasted for several hours thereafter.”
From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Liang et al, 1992b
The Results report a dose-dependent increase beginning about 30 minutes after infusion, and the Discussion says the effect lasted at least 6 hours. However, the Discussion places its maximum at about 80–90 minutes, so the claim that startle grew steadily throughout the 2-hour test overstates the time course. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPretreatment with the CRF antagonist α-helical CRF blocks CRF-induced startle increases, and delayed infusions of it reverse them.
“These increases were prevented by pretreatment with α-helical CRF (αhCRF9–41), a CRF antagonist, and were reversed by delayed αhCRF9–41 infusions”
From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Liang et al, 1992b
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- Authors
- Liang, K., Melia, K., Miserendino, M., Falls, W., Campeau, S., & Davis, M.
- Affiliations
- Yale University (US)
- ORCID
- Campeau, S
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1992-06-01
- Volume
- 12
- Issue
- 6
- Pages
- 2303-2312
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6575911
- OpenAlex
- W1637259485
- Cited by
- 203
- References
- 6
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 9 · 2012: 4
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council
- National Institutes of Health (5r01ns018033-06)
- National Institute of Mental Health (MH 25642, MH 47840, P01MH025642)
- National Institute of Neurological Disorders and Stroke (NS-18033)
- Air Force Office of Scientific Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- corticotropin-releasing factor, acoustic startle response, intracerebroventricular infusion, CRF antagonist, sympathetic activation, hexamethonium, chlorisondamine, fear, anxiety, startle habituation
- MeSH terms
- Acoustic Stimulation, Analysis of Variance, Animals, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Ganglionic Blockers, Injections, Intraventricular, Male, Rats, Inbred Strains, Reflex, Startle, Time Factors, Rats
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