Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Young, June M; McGregor, Iain S.; Mallet, Paul E.

doi:10.1038/sj.npp.1300692

Cited by 25 publications

(31 citation statements)

References 53 publications

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“…Previous studies utilizing measures of accuracy often observed acute reductions of accuracy in working memory tasks (e.g. Braida et al, 2002; Galizio et al, 2009; Young, McGregor & Mallet, 2005), reference memory tasks (e.g. Kay et al, 2010), or both.…”

Section: Discussionmentioning

confidence: 99%

Effects of MDMA on olfactory memory and reversal learning in rats

Hawkey

April

Galizio

2014

Neurobiology of Learning and Memory

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The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0 mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0 mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions.

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Section: Discussionmentioning

confidence: 99%

Effects of MDMA on olfactory memory and reversal learning in rats

Hawkey

April

Galizio

2014

Neurobiology of Learning and Memory

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“…Δ 9 ‐THC also undergoes additive or synergistic interactions in mice with nicotine for the production of conditioned place preference, hypothermia and hypolocomotion (Valjent et al. , 2002), with 3,4‐methylenedioxymethamphetamine (MDMA) in conditioned place preference, self‐administration and working memory paradigms (Young et al. , 2005; Robledo et al.…”

Section: Multi‐targetingmentioning

confidence: 99%

“…• reduction of nociceptive scratching behaviour induced in rats by injection of formalin into the temporomandibular joint Neither of these compounds displayed antinociceptive activity by itself and their ability to potentiate R-(+)-WIN55212 did not extend to the COX-1-selective inhibitor, SC-560. D 9 -THC also undergoes additive or synergistic interactions in mice with nicotine for the production of conditioned place preference, hypothermia and hypolocomotion (Valjent et al, 2002), with 3,4-methylenedioxymethamphetamine (MDMA) in conditioned place preference, self-administration and working memory paradigms (Young et al, 2005;Robledo et al, 2007) and, for the production of catalepsy or hypothermia in mice or rats, with a range of non-cannabinoids that in addition to opioids, nicotine, and MDMA include benzodiazepines, prostaglandins, reserpine and ligands that target muscarinic cholinoceptors or some types of dopamine, noradrenaline, 5-hydroxytryptamine or g-aminobutyric acid receptors as agonists or antagonists (Marchese et al, 2003;review by Pertwee, 1992).…”

Section: Cannabinoid Receptor Agonistmentioning

confidence: 99%

Emerging strategies for exploiting cannabinoid receptor agonists as medicines

Pertwee

2009

British J Pharmacology

380

353

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Medicines that activate cannabinoid CB1 and CB2 receptor are already in the clinic. These are Cesamet ® (nabilone), Marinol ® (dronabinol; D 9-tetrahydrocannabinol) and Sativex ® (D 9-tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol ® can also be prescribed to stimulate appetite, while Sativex ® is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB2 receptors; or (v) 'multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed.

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“…Two previous studies reported on the effects of acute co-administration of THC and MDMA in adult rats (Morley et al , 2004; Young et al , 2005), and more recently Robledo and coworkers (2007) examined both the acute neurochemical effects of THC and MDMA co-administration and the combined effects of these compounds in a conditioned place paradigm in mice. However, to our knowledge there is no published information regarding the consequences of recurrent adolescent co-administration of these compounds in a rodent model.…”

Section: Introductionmentioning

confidence: 99%

Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats

2011

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Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or “ecstasy”) also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ9-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5 mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA.

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Co-administration of THC and MDMA (‘Ecstasy’) Synergistically Disrupts Memory in Rats

Cited by 25 publications

References 53 publications

Effects of MDMA on olfactory memory and reversal learning in rats

Effects of MDMA on olfactory memory and reversal learning in rats

Emerging strategies for exploiting cannabinoid receptor agonists as medicines

Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats

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