The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice
Open accessAbstract
Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS exposures trigger two opposing processes: (1) fear extinction, which is favored by CS massing, and (2) fear incubation (increase), which is favored by spacing. We here report the effects of manipulating the adrenergic system during massed or spaced CS presentations in fear-conditioned mice. We administered yohimbine (5 mg/kg), an alpha(2)-receptor antagonist, or propranolol (10 mg/kg), a beta-receptor antagonist, systemically prior to CS presentation sessions and recorded both short- and long-term changes in conditional freezing. Yohimbine treatment facilitated extinction of both cue and context fear with massed protocols. When given before spaced CS presentations, propranolol led to a persistent incubation of cue fear, whereas yohimbine led to persistent extinction, compared with vehicle-treated animals, which showed no change in fear. These results suggest that norepinephrine positively modulates the formation of fear extinction memories in mice. They also provide clear evidence that spaced CS presentations trigger both fear-reducing (extinction) and fear-increasing (incubation) mechanisms.
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“Notably, previous existing studies have mainly tested the inhibitory learning model using conditioning paradigms with rodents (e.g. Berman and Dudai, 2001; Cain et al., 2004; Harris and Westbrook, 1998; McNally, 2005), or human non-clinical samples (e.g. Eifert and Heffner, 2003; Karekla et al., 2004).”
From Feeling more confident to encounter negative emotions: The mediating role of distress tolerance on the relationship between self-efficacy and outcomes of exposure and response prevention for OCD (2024) · cites this paper as Cain et al., 2004
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Maximizing exposure therapy: An inhibitory learning approach
Craske, M. G., Treanor, M., Conway, C. C., Zbozinek, T., & Vervliet, B. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.04.006 · Cited by 2,339
“Notably, sustained arousal throughout extinction is associated with less fear at retest in animals (Rescorla, 2006) and in humans (Culver, Stephans & Craske, under review), arousal consolidates extinction memories (Cain et al., 2004) and in several of our studies, failure to habituate throughout exposure therapy was n…”
Neural Mechanisms of Extinction Learning and Retrieval
Quirk, G. J., & Mueller, D. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301555 · Cited by 1,645
Optimizing inhibitory learning during exposure therapy
Craske, M. G., Kircanski, K., Zelikowsky, M., Mystkowski, J., Chowdhury, N., & Baker, A. (2008) · Behaviour Research and Therapy · doi:10.1016/j.brat.2007.10.003 · Cited by 1,607
Myers, K. M., & Davis, M. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001939 · Cited by 1,277
Prefrontal mechanisms in extinction of conditioned fear
Quirk, G. J., Garcia, R., & González-Lima, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.010 · Cited by 682
Metadata
- Authors
- Cain, C. K., Blouin, A. M., & Barad, M.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Cain, Christopher K.
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-03
- Volume
- 11
- Issue
- 2
- Pages
- 179-187
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC379688
- OpenAlex
- W2067602621
- Cited by
- 215
- References
- 66
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 21 · 2014: 17 · 2013: 17 · 2012: 12
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (F31MH065809)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fear extinction, adrenergic system, norepinephrine, yohimbine, propranolol, alpha2-adrenoceptors, beta-adrenergic receptors, contextual fear, freezing behavior, fear conditioning, mice
- MeSH terms
- Adrenergic Agonists, Animals, Association Learning, Conditioning, Classical, Extinction, Psychological, Fear, Male, Memory, Mice, Inbred C57BL, Synaptic Transmission, Norepinephrine, Propranolol, Yohimbine, Immobility Response, Tonic, Mice
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