A cannabinoid CB(1) receptor antagonist ameliorates impairment of recognition memory on withdrawal from MDMA (Ecstasy).
Yoko Nawata, Takato Hiranita, Tsuneyuki Yamamoto
Neuropsychopharmacology January 2010 DOI: 10.1038/npp.2009.158 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | MDMA AM251 |
| Dose | MDMA 10 mg/kg i.p. once daily for 7 days; AM251 administered 30 min before training or co-administered with MDMA (dose not stated) |
| Duration | 7-day MDMA administration, testing on 7th day of withdrawal |
| Measures | novel object recognition task, western blotting |
| Topics | MDMA |
| Key findings | MDMA withdrawal impaired novel object recognition in mice and increased hippocampal CB(1) receptor protein; AM251 blocked both effects, and CB(1) knockout mice showed no impairment, suggesting hippocampal CB(1) receptor activation underlies the cognitive deficit. |
Abstract
(+/-)-3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') abusers have persistent neuropsychiatric deficits including memory impairments after the cessation of abuse. On the other hand, cannabinoid CB(1) receptors have been implicated in learning/memory, and are highly expressed in the hippocampus, a region of the brain believed to have an important function in certain forms of learning and memory. In this study, we clarified the mechanism underlying the cognitive impairment that develops during MDMA withdrawal from the standpoint of the cannabinoid CB(1) receptors. Mice were administered MDMA (10 mg/kg, i.p.) once a day for 7 days. On the 7th day of withdrawal, a novel object recognition task was performed and the amount of cannabinoid CB(1) receptor protein was measured with western blotting. Recognition performance was impaired on the 7th day of withdrawal. This impairment was blocked by AM251, a cannabinoid CB(1) receptor antagonist, administered 30 min before the training trial or co-administered with MDMA. At this time, the level of cannabinoid CB(1) receptor protein increased significantly in the hippocampus but not the prefrontal cortex or striatum. This increase of CB(1) receptor protein in the hippocampus was also blocked by the co-administration of AM251. Furthermore, CB(1) receptor knockout mice showed no impairment of recognition performance on the withdrawal from MDMA. The impairment of recognition memory during withdrawal from MDMA may result from the activation of cannabinoid CB(1) receptors in the hippocampus.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- 3,4-Methylenedioxymethamphetamine (MDMA) impairs cognitive function during withdrawal via activation of the arachidonic acid cascade in the hippocampus. Drug and Alcohol Dependence April 1, 2024
- A Systematic Review of the MDMA Model to Address Social Impairment in Autism. Current Neuropharmacology 2021
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Cites 7
- Patterns of Memory Dysfunction in Current and 2-year Abstinent MDMA Users Journal of Clinical and Experimental Neuropsychology March 21, 2006
- CB1 cannabinoid receptor modulates 3,4-methylenedioxymethamphetamine acute responses and reinforcement. Biological Psychiatry June 1, 2008
- Signaling via CNS cannabinoid receptors. Molecular and cellular endocrinology April 16, 2008
- Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. Learning & Memory 2007
- Chronic MDMA (ecstasy) use, cognition and mood. Psychopharmacology May 2004
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