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Immunohistochemical Analyses of Long-Term Extinction of Conditioned Fear in Adolescent Rats
Abstract
Adolescence is a period of heightened emotional reactivity and vulnerability to poor outcomes (e.g., suicide, anxiety, and depression). Recent human and animal neuroimaging studies suggest that dramatic changes in prefrontal cortical areas during adolescence are involved in these effects. The present study explored the functional implications of prefrontal cortical changes during adolescence by examining conditioned fear extinction in adolescent rats. Experiment 1 showed that preadolescent (i.e., postnatal day [P] 24), adolescent (P35), and adult (P70) rats express identical extinction acquisition following 3 white-noise conditioned stimulus (CS) and shock pairings. When tested the next day, however, adolescent rats showed almost complete failure to maintain extinction of CS-elicited freezing compared with P24 and P70 rats. It was observed in experiment 2 that following extinction, P24 and P70 rats express significantly elevated levels of phosphorylated mitogen-activated protein kinase (pMAPK) in the infralimbic cortex (IL) compared with adolescent rats. Interestingly, adolescent rats successfully exhibited long-term extinction if the amount of extinction training was doubled (experiment 3). More extinction training also led to increased phosphorylation of MAPK in the IL in these rats. These findings suggest that adolescents are less efficient in utilizing prefrontal areas, which may lead to an impairment in the maintenance of extinguished behavior.
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“adolescents showed markedly impaired retention of the extinction, thereby spontaneously reinstating their fear to CS presentation (McCallum et al, 2010; Kim et al, 2011).”
From Rewards, aversions and affect in adolescence: emerging convergences across laboratory animal and human data (2011) · cites this paper as Kim et al, 2011
In the citing paper
“For example, adolescents continue to show signs of defensive responding to previously learned threat cues (freezing in rodents and elevated skin conductance in humans), suggesting an age-specific relative dysregulation of the process that updates threat associations as safe7,10–13.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [10]
In the citing paper
“Immunohistochemical evidence points to reduced synaptic plasticity in areas of the mPFC after extinction recall in adolescent rodents7,10.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [10]
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“Recent research with rodents and humans has shown distinctive developmental profiles of blunted threat extinction recall in adolescents6–11, relative to children and adults.”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [10]
In the citing paper
“The analysis of extinction over time (Stimulus × Time × Age interaction), showed increased recruitment of the mPFC to CS+ vs. CS− in the early trials for older participants and in the late trials for younger participants (see Fig. 2 and Table 1).”
From Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood (2019) · cites this paper as [10]
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Metadata
- Authors
- Kim, J. H., Li, S., & Richardson, R.
- Affiliations
- UNSW Sydney (AU)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-06-24
- Volume
- 21
- Issue
- 3
- Pages
- 530-538
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2159947310
- Cited by
- 149
- References
- 57
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 4 · 2021: 10 · 2020: 14 · 2019: 15 · 2018: 7 · 2017: 12 · 2016: 12 · 2015: 13 · 2014: 10 · 2013: 11 · 2012: 6
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Research Council (DP0985554)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- adolescence, prefrontal cortex, infralimbic cortex, mitogen-activated protein kinase, MAPK phosphorylation, freezing behavior, late childhood, anxiety vulnerability
- MeSH terms
- Age Factors, Animals, Conditioning, Classical, Extinction, Psychological, Fear, Immunohistochemistry, Male, Phosphorylation, Rats, Sprague-Dawley, Prefrontal Cortex, Mitogen-Activated Protein Kinase Kinases, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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