A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

Nawata, Yoko; Hiranita, Takato; Yamamoto, Tsuneyuki

doi:10.1038/npp.2009.158

Cited by 26 publications

(21 citation statements)

References 36 publications

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“…Nawata et al also showed that CB1 receptor antagonist attenuated the MDMA-induced cognitive deficit in mice [43]. Accordingly, we observed in the present study that genes involved in the regulation of memory and cognitive processes were downregulated after MDMA treatment in DA rats.…”

Section: Discussionsupporting

confidence: 72%

RETRACTED ARTICLE: Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

et al. 2013

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Background3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions, impairments frequently described in heavy MDMA users. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier.ResultsThe number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory’ and 'cognition’, 'dendrite development’ and 'regulation of synaptic plasticity’ gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid- and Epha4, Epha5, Epha6 ephrin receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development’, 'regulation of synaptic plasticity’ and 'positive regulation of synapse assembly’ gene sets were upregulated. Changes in the dorsal raphe region were mild and in most cases not significant.ConclusionThe present data raise the possibility of new synapse formation/synaptic reorganization in the frontal cortex three weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is suggested by the data, which underlines the particular vulnerability of this brain region after the drug treatment. Finally, our results also suggest the substantial contribution of CB1 receptor and endocannabinoid mediated pathways in the hippocampal impairments. Taken together the present study provides evidence for the participation of new molecular candidates in the long-term effects of MDMA.

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Section: Discussionsupporting

confidence: 72%

RETRACTED ARTICLE: Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

et al. 2013

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“…Cannabinoid CB1 receptors (CB1R) 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. Using male CD1 wt and CB1R knockout (CB1R -/-) mice, Nawata and colleagues investigated the effect of withdrawal from repeated MDMA in an object recognition test [97]. Similar to what had been observed by others in rats [98][99][100], wt mice showed impaired recognition memory upon MDMA withdrawal.…”

Section: Ii5 Cognitive and Behavioural Impairmentsmentioning

confidence: 80%

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Stove¹,

Letter²,

Piette³

et al. 2010

CPB

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The party drug 3,4-methylenedioxymethamphetamine -better known as MDMA or ecstasy-has numerous effects on the human body, characterized by a rush of energy, euphoria and empathy. However, also a multitude of toxic/neurotoxic effects have been ascribed to MDMA, based upon case reports and studies in animals. Given the intrinsic difficulties associated with controlled studies in human beings, most of our insights into the biology of MDMA have been gained through animal studies. The vast majority of these studies utilizes a pharmacological approach to elucidate the mechanisms by which MDMA exerts its effects.Advances in genetics during the last decade have led to the development of several mouse models (transgenic or knockout) that have greatly contributed to our understanding of MDMA biology. This review provides an overview of these genetically modified animal models, in the light of some characteristic effects of MDMA, e.g. hyperlocomotion, neurotoxicity, hyperthermia, behaviour or rewarding. Without a shadow of a doubt, the next decade will bring many more advanced animal models, such as mice with site-specific deletion or rescue of genes and more genetically modified rat models. These models will further improve our knowledge on the pharmacology and toxicity of MDMA and, possibly, may assist in developing therapies coping with potential damage in abusers of MDMA and other drugs, as well as in patients suffering from specific neuronal pathologies.MDMA in advanced animal models 3

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“…There are also some reports on induced memory dysfunction by this agent remaining after abstinence. In an object recognition task, memory was significantly impaired after withdrawal of repeated, but not single administration of MDMA on 1st and especially 7th day of withdrawal period in mice (40). In a comparison among abstinent rats after chronic use of MDMA, current cannabinoid and control groups showed that abstinent MDMA animals were the worst group in memory tests (41).…”

Section: Resultsmentioning

confidence: 97%

“…In an object recognition memory task, chronic intake of AM281, a cannabinoid antagonist/inverse agonist, significantly improved the memory impairment following naloxone-precipitated morphine withdrawal in mice (73). Nawata et al (40) showed that levels of cannabinoid CB1 receptor protein increased on the 7th day of withdrawal, but not on the first day after chronic use of MDMA. Prescribing a CB1 antagonist with MDMA and AM251, for mice prevented memory deficits observed in withdrawn animals by using an objective recognition task.…”

Section: Resultsmentioning

confidence: 99%

“…Prescribing a CB1 antagonist with MDMA and AM251, for mice prevented memory deficits observed in withdrawn animals by using an objective recognition task. Nevertheless, mice devoid of the CB1 receptor subtype showed no impairment in memory cognition after withdrawal of MDMA (40). Gonzalez et al (74) found that cocaine exerted minor impacts on cannabinoid system in different regions of brain.…”

Section: Resultsmentioning

confidence: 99%

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Learning and Memory Performance After Withdrawal of Agent Abuse: A Review

Amin

Andalib

Vaseghi

et al. 2016

IJPBS

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ContextAgent abuse is a dire predicament worldwide. Learning and memory deficits stemming from the withdrawal of such agents is an increasingly burning issue for researchers.Evidence AcquisitionThe present review revisits the literature generated by far pertaining to the research on memory and cognition deficiencies after withdrawal of agent abuse and corresponding mechanisms.ResultsDeficiency on spatial memory, episodic memory and working memory are common after withdrawal of agent abuse.ConclusionsThe present review suggests that memory dysfunction may result from withdrawal of agent abuse.

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A Cannabinoid CB1 Receptor Antagonist Ameliorates Impairment of Recognition Memory on Withdrawal from MDMA (Ecstasy)

Cited by 26 publications

References 36 publications

RETRACTED ARTICLE: Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

RETRACTED ARTICLE: Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats

Mice in Ecstasy: Advanced Animal Models in the Study of MDMA

Learning and Memory Performance After Withdrawal of Agent Abuse: A Review

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