Short- and long-term effects of cannabinoids on the extinction of contextual fear memory in rats
Abstract
Facilitation of memory extinction by manipulation of the endocannabinoid (eCB) system has been recently studied in several paradigms. Our previous results pointed to facilitation of contextual fear memory extinction by a low dose of a cannabinoid agonist, with a suggestion of short-term effects. The aim of the present study was to further investigate the effects of cannabinoid drugs in the short- and long-term extinction of conditioned fear using an extended extinction protocol. Male Wistar rats were placed in a conditioning chamber and after 3min received a footshock (1.5mA, 1s). On the next day, they received i.p. drug treatment (WIN55212-2 0.25mg/kg, AM404 10mg/kg, SR141716A 1mg/kg) and were re-exposed to the conditioning chamber for 30min (extinction training). No-Extinction groups received the same drug treatment, but were exposed for 3min to the conditioning chamber. A drug-free test of contextual memory (3min) was performed 7 days later. The cannabinoid agonist WI55212-2 and the inhibitor of eCB metabolism/uptake AM404 facilitated short-term extinction. In addition, long-term effects induced by treatments with WIN55212 and AM404 were completely divergent to those of SR141716A treatment. The present results confirm and extend previous findings showing that the eCB system modulates short-term fear memory extinction with long-lasting consequences.
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Augmenting levels of anandamide in the amygdala modulates short-term fear extinction.
“Augmenting levels of anandamide in the amygdala modulates short-term fear extinction9”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [9]
Activating CB1R via systemic or intra-hippocampal or intra-mPFC administration of WIN55212-2, AM404, or AEA facilitates rodent fear extinction, in most cases without affecting conditioned fear.
“Activating CB1R via systemic or intra-hippocampal or -mPFC administration of either the CB1R agonist, WIN55212-2, the ECB reuptake blocker, AM404, or AEA itself has been shown to facilitate rodent fear extinction, in most cases without affecting conditioned fear [89,95–98] (but see [90]).”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [95]
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Self-citation
- Authors
- Pamplona, F. A., Bitencourt, R. M., & Takahashi, R. N.
- Affiliations
- Universidade Federal de Santa Catarina (BR)
- Corresponding author
- Takahashi, Reinaldo N.
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 90
- Issue
- 1
- Pages
- 290-293
- ISSN
- 1074-7427 (ISSN-L)
- OpenAlex
- W2001442529
- Cited by
- 123
- References
- 18
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 7 · 2014: 9 · 2013: 12 · 2012: 12
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sanofi
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Universidade Federal de Santa Catarina
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- cannabinoids, endocannabinoid system, fear extinction, contextual fear memory, WIN 55,212-2, AM404, SR141716A, cannabinoid receptor agonists, cannabinoid receptor antagonists, long-term memory effects
- MeSH terms
- Rimonabant, Animals, Arachidonic Acids, Calcium Channel Blockers, Cannabinoids, Conditioning, Psychological, Extinction, Psychological, Fear, Male, Memory, Morpholines, Naphthalenes, Piperidines, Pyrazoles, Time Factors, Rats, Wistar, Freezing Reaction, Cataleptic, Benzoxazines, Rats
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