Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling
Abstract
The role of endocannabinoid (eCB) signalling in restraint stress-induced neuronal activation was studied. Male mice exposed to 30 min of restraint exhibit increased Fos protein within prefrontal cortex (PFC), lateral septum (LS), nucleus accumbens (Acb) and medial amygdala. SR141716 (2 mg/kg) itself had no effect on Fos but pretreatment with SR141716 significantly potentiated restraint-induced Fos expression in cingulate, LS and Acb. SR141716 also significantly increased the time spent in active escape behaviours during the restraint. In restraint-habituated mice (mice exposed to four previous restraint episodes), the fifth restraint exposure resulted in decreased expression of active escape behaviours compared to the first exposure and only induced Fos protein in the central and medial amygdala. Administration of SR141716 prior to the fifth restraint episode resulted in greater potentiation of restraint-induced Fos induction than the first; significant increases occurred within all regions of PFC examined, LS and Acb. Brain regional eCB content was measured immediately after restraint. N-arachidonylethanolamine content within the amygdala was significantly decreased after both restraint episodes. 2-Arachidonylglycerol content was significantly increased in both the limbic forebrain and amygdala after the fifth restraint but not the first. Restraint had no effect on cerebellar eCB content. These data suggest that eCB activation of CB(1) receptors opposes the behavioural and neuronal responses to aversive stimuli. Because repeated homotypic stress increased both limbic 2-AG and resulted in a greater effect of SR141716 on limbic Fos expression, we hypothesize that increased CB(1) receptor activity contributes to the expression of habituation to homotypic stress.
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Stress produces divergent effects on AEA and 2-AG levels in the BLA, with an elevation in 2-AG levels and a rapid induction of FAAH activity and resultant decline in the AEA pool following exposure to various types of stress.
“Interestingly, stress appears to produce divergent effects on AEA and 2-AG levels in the BLA – with an elevation in 2-AG levels [57], but a rapid induction of FAAH activity and a resultant decline in the pool of AEA [58–60] were reported following exposure to various types of stress.”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [60]
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- Authors
- Patel, S., Roelke, C. T., Rademacher, D. J., & Hillard, C. J.
- Affiliations
- Medical College of Wisconsin (US)
- Corresponding author
- Hillard, Cecilia J.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2005-02
- Volume
- 21
- Issue
- 4
- Pages
- 1057-1069
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1901285090
- Cited by
- 297
- References
- 51
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 25 · 2020: 9 · 2019: 14 · 2018: 15 · 2017: 19 · 2016: 17 · 2015: 23 · 2014: 11 · 2013: 15 · 2012: 13
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute on Drug Abuse (R01DA016967, DA016967)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- endocannabinoid signaling, restraint stress, CB1 receptor, SR141716, Fos expression, 2-arachidonoylglycerol, anandamide, escape behavior, prefrontal cortex, lateral septum, nucleus accumbens, medial amygdala, aversive stimuli, limbic system
- MeSH terms
- Rimonabant, Analysis of Variance, Animals, Behavior, Animal, Brain Chemistry, Cell Count, Chromatography, High Pressure Liquid, Escape Reaction, Immunohistochemistry, Male, Mice, Inbred ICR, Neural Inhibition, Piperidines, Pyrazoles, Restraint, Physical, Mass Spectrometry, Stress, Psychological, Time Factors, Signal Transduction, Oncogene Proteins v-fos, Mice, Cannabinoid Receptor Modulators, Cannabinoid Receptor Antagonists
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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