Circadian genes P eriod 1 and P eriod 2 in the nucleus accumbens regulate anxiety‐related behavior
Open accessAbstract
It has been suggested for some time that circadian rhythm abnormalities underlie the development of multiple psychiatric disorders. However, it is unclear how disruptions in individual circadian genes might regulate mood and anxiety. Here we found that mice lacking functional mP eriod 1 (mP er1) or mP eriod 2 (mP er2) individually did not have consistent behavioral abnormalities in measures of anxiety‐related behavior. However, mice deficient in both mP er1 and mP er2 had an increase in levels of anxiety‐like behavior in multiple measures. Moreover, we found that mP er1 and mP er2 expression was reduced in the nucleus accumbens (NA c) after exposure to chronic social defeat stress, a paradigm that led to increased anxiety‐related behavior. Following social defeat, chronic treatment with fluoxetine normalized P er gene expression towards wild‐type levels. Knockdown of both mP er1 and mP er2 expression via RNA interference specifically in the NA c led to a similar increase in anxiety‐like behavior as seen in the mutant animals. Taken together, these results implicate the P er genes in the NA c in response to stress and the development of anxiety.
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Mice lacking both Per1 and Per2 display elevated anxiety-like behavior, whereas mice lacking either Per1 or Per2 do not have altered anxiety-like responses.
“In contrast, mice lacking both Per1 and Per2 display elevated anxiety-like behavior, whereas mice lack either Per1 or Per2 do not have altered anxiety-like responses103.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [103]
The Discussion reports a robust increase in anxiety-related behavior in mice lacking both mPer1 and mPer2. But it also says single-gene mutants showed greater anxiety-like behavior on a restricted subset of measures; the Results report a significant decrease in open-arm time for mPer2 single mutants. Thus, the claim that neither single mutant has altered anxiety-like responses is too categorical. Page numbers are not provided in our copy. (LLM, conf=0.92)
Experimental — accuracy not yet measuredInhibition of Per1/Per2 expression in the nucleus accumbens (NAc) of wild-type mice produces anxiety-like behavior, suggesting a causal role for these core clock components in the NAc for regulating anxiety.
“Inhibition of Per1/Per2 expression in the nucleus accumbens (NAc) of wild-type mice also produces anxiety-like behavior, suggesting a causal role for these core clock components in the NAc for regulating anxiety.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [103]
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“This phenotype is similar to that of Clock∆19 mutant mice, which exhibit reduced anxiety-like behaviors and is the opposite of the Per1/Per2 double mutant, which exhibit increased anxiety-like behavior (Roybal et al., 2007; Spencer et al., 2013).”
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- Authors
- Spencer, S., Falcon, E., Kumar, J., Krishnan, V., Mukherjee, S., Birnbaum, S. G., & McClung, C. A.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Department of Psychiatry UT Southwestern Medical Center Dallas TX USA
- University of Pittsburgh (US)
- Corresponding author
- McClung, Colleen A.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2012-10-08
- Volume
- 37
- Issue
- 2
- Pages
- 242-250
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC3711746
- OpenAlex
- W2114527998
- Cited by
- 113
- References
- 60
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 10 · 2021: 11 · 2020: 11 · 2019: 4 · 2018: 6 · 2017: 10 · 2016: 4 · 2015: 12 · 2014: 7 · 2013: 5
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH082876, MH082876, F31MH090683)
- National Institute on Drug Abuse (R01DA023988)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- circadian genes, Period2, mPer1, mPer2, nucleus accumbens, anxiety-like behavior, social defeat stress, fluoxetine, RNA interference, circadian rhythm, mood disorders
- MeSH terms
- Animals, Anxiety, Avoidance Learning, Fluoxetine, Mice, Inbred C57BL, Mice, Mutant Strains, Mutation, Nucleus Accumbens, Stress, Psychological, Transcription, Genetic, Antidepressive Agents, Second-Generation, Maze Learning, RNA, Small Interfering, Mice, Period Circadian Proteins
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