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Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

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Cain, Christopher K., Blouin, Ashley M., Barad, Mark·2004·Learning & Memory

DOI 10.1101/lm.71504PMC PMC379688

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Abstract

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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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
DOI: 10.1101/lm.71504
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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Adrenergic Transmission Facilitates Extinction of Conditional Fear in Mice

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