The cannabinoid receptor CB1 inverse agonist AM251 potentiates the anxiogenic activity of urocortin I in the basolateral amygdala
Abstract
The basolateral amygdala is reported to play an important role in the neural bases of emotional processing. Previous studies have shown that injections of urocortin I (UcnI) into the basolateral amygdala (BLA) elicit anxiety-like behaviors in animal models. The present study examined the anxiogenic effects of UcnI administered directly into the BLA of male Sprague-Dawley rats. UcnI was administered at doses of 0.1-10.0 pmol and rats were then placed in an elevated plus maze for 10 min. UcnI reliably decreased the percent time spent in the open arms of the elevated plus maze (EPM) as well as open arm entries. This effect was observed across all doses tested, indicating the induction of anxiety-like behavior. In separate groups of rats, the CB(1) inverse agonist AM251 was administered systemically (0.03-3.0 mg/kg IP) or directly into the BLA (0.25-25.0 pmol) and EPM performance assessed. Both routes of AM251 administration produced a reduction in open arm entries and in time spent in the open arms. Moreover, when rats were pretreated with AM251 either systemically or directly into the BLA, the anxiogenic effect of UcnI was potentiated. That is, co-administration of AM251 and UcnI produced a greater suppression of percent time spent in the open arms and open arm entries as compared to UcnI alone. Based on these findings, we propose that urocortin and endocannabinoid signaling are part of an integrated neural axis modulating anxiety states within the basolateral amygdala. This article is part of a Special Issue entitled 'Anxiety and Depression'.
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CB1R antagonism increases BLA excitability, activates the HPA axis, and increases anxiety-like behavior.
“First, presumably by removing AEA-mediated tonic inhibitory activity, CB1R antagonism increases BLA excitability [61–63], activates the hypothalamic–pituitary–adrenal (HPA) axis and increases anxiety-like behavior [58,64,65].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [64]
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Kochenborger, L., Levone, B. R., da Silva, E. S., Taschetto, A. P. D., Terenzi, M. G., Paschoalini, M. A., & Faria, M. S. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.05.017 · Cited by 9 · see citing works
CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin.
Hassanzadeh, P., & Rostami, F. (2014) · Europe PMC (PubMed Central) · Cited by 6 · see citing works
Aliczki, M., & Haller, J. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2294-9_4 · Cited by 5 · see citing works
Fimmel, A. I., Dono, L. M., Yee, M. N., & Currie, P. J. (2014) · Journal of Behavioral and Brain Science · doi:10.4236/jbbs.2014.42013 · Cited by 1 · see citing works
Dirks, A. (2017) · SSRN Electronic Journal · doi:10.2139/ssrn.2974377
Parker, L. A. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734674759.793560175
Endocannabinoids and the neurobiology of emotional states
Petrie, G. N., Lunge, A. R., Mayo, L. M., & Hill, M. N. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-13908-6.00021-9
- Authors
- Dono, L. M., & Currie, P. J.
- Affiliations
- Reed College (US)
- Corresponding author
- Currie, Paul J.
- ORCID
- Currie, Paul J.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 62
- Issue
- 1
- Pages
- 192-199
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2093818423
- Cited by
- 32
- References
- 73
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 7 · 2012: 2
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- AM251, basolateral amygdala, anxiety-like behavior, endocannabinoid signaling, corticotropin-releasing factor, elevated plus maze, emotional processing
- MeSH terms
- Amygdala, Animals, Anxiety, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, Exploratory Behavior, Male, Piperidines, Pyrazoles, Anti-Anxiety Agents, Rats, Sprague-Dawley, Maze Learning, Rats, Urocortins
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