Cannabinoids modulate hippocampal memory and plasticity
Abstract
Considerable evidence demonstrates that cannabinoid agonists impair whereas cannabinoid antagonists improve memory and plasticity. However, recent studies suggest that the effects of cannabinoids on learning do not necessarily follow these simple patterns, particularly when emotional memory processes are involved. We investigated the involvement of the cannabinoid system in hippocampal learning and plasticity using the fear‐related inhibitory avoidance (IA) and the non‐fear‐related spatial learning paradigms, and cellular models of learning and memory, i.e., long‐term potentiation (LTP) and long‐term depression (LTD). We found that microinjection into the CA1 of the CB1/CB2 receptor agonist WIN55,212‐2 (5 μg/side) and an inhibitor of endocannabinoid reuptake and breakdown AM404 (200 ng/side) facilitated the extinction of IA, while the CB1 receptor antagonist AM251 (6 ng/side) impaired it. WIN55,212‐2 and AM251 did not affect IA conditioning, while AM404 enhanced it, probably due to a drug‐induced increase in pain sensitivity. However, in the water maze, systemic or local CA1 injections of AM251, WIN55,212‐2, and AM404 all impaired spatial learning. We also found that i.p. administration of WIN55,212‐2 (0.5 mg/kg), AM404 (10 mg/kg), and AM251 (2 mg/kg) impaired LTP in the Schaffer collateral‐CA1 projection, whereas AM404 facilitated LTD. Our findings suggest diverse effects of the cannabinoid system on CA1 memory and plasticity that cannot be categorized simply into an impairing or an enhancing effect of cannabinoid activation and deactivation, respectively. Moreover, they provide preclinical support for the suggestion that targeting the endocannabinoid system may aid in the treatment of disorders associated with impaired extinction‐like processes, such as post‐traumatic stress disorder. © 2009 Wiley‐Liss, Inc.
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WIN administered into the CA1 facilitates IA extinction.
“We have recently shown that WIN administered into the CA1 facilitates IA extinction, with no effect on conditioned avoidance (Abush and Akirav, 2010).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as Abush and Akirav, 2010
WIN administered into the CA1 has no effect on conditioned avoidance.
“We have recently shown that WIN administered into the CA1 facilitates IA extinction, with no effect on conditioned avoidance (Abush and Akirav, 2010).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as Abush and Akirav, 2010
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Stress modulation of reconsolidation
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Lights on Endocannabinoid-Mediated Synaptic Potentiation
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- Authors
- Abush, H., & Akirav, I.
- Affiliations
- University of Haifa (IL)
- Corresponding author
- Akirav, Irit
- ORCID
- Akirav, Irit
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2009-10-14
- Volume
- 20
- Issue
- 10
- Pages
- 1126-1138
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- OpenAlex
- W1987625703
- Cited by
- 186
- References
- 68
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 8 · 2021: 13 · 2020: 8 · 2019: 6 · 2018: 10 · 2017: 15 · 2016: 15 · 2015: 18 · 2014: 14 · 2013: 12 · 2012: 25
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabinoids, endocannabinoid system, CA1, memory, synaptic plasticity, passive avoidance, fear extinction, spatial learning, long-term potentiation, long-term depression, CB1 receptor, CB2 receptor, WIN 55,212-2, AM404, AM251, post-traumatic stress disorder
- MeSH terms
- Animals, Avoidance Learning, Cannabinoids, Hippocampus, Learning, Male, Memory, Memory Disorders, Microinjections, Neuronal Plasticity, Rats, Sprague-Dawley, Rats, CA1 Region, Hippocampal, Cannabinoid Receptor Modulators
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