Behavioural and neurochemical effects of combined MDMA and THC administration in mice

Robledo, Patricia; Trigo, J.M.; Panayi, Fany; Torre, Rafael de la; Maldonado, Rafaël

doi:10.1007/s00213-007-0879-8

Cited by 36 publications

(28 citation statements)

References 32 publications

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“…THC and AEA facilitate dopamine release in the nucleus accumbens (NAc) in rats (Chen et al, 1990(Chen et al, , 1991Tanda et al, 1997;Cheer et al, 2004;Solinas et al, 2006; and mice (Robledo et al, 2007). These findings are consistent with the idea that CB 1 receptor stimulation enhances reinforced behavior mediated by the mesolimbic dopamine system.…”

Section: Introductionsupporting

confidence: 78%

Δ⁹-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Wiebelhaus

Grim

Owens

et al. 2014

J Pharmacol Exp Ther

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A growing body of evidence implicates endogenous cannabinoids as modulators of the mesolimbic dopamine system and motivated behavior. Paradoxically, the reinforcing effects of D 9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, have been difficult to detect in preclinical rodent models. In this study, we investigated the impact of THC and inhibitors of the endocannabinoid hydrolytic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) on operant responding for electrical stimulation of the medial forebrain bundle [intracranial self-stimulation (ICSS)], which is known to activate the mesolimbic dopamine system. These drugs were also tested in assays of operant responding for food reinforcement and spontaneous locomotor activity. THC and the MAGL inhibitor JZL184 (4-[bis(1,3-benzodioxol-5-yl) hydroxymethyl]-1-piperidinecarboxylic acid 4-nitrophenyl ester) attenuated operant responding for ICSS and food, and also reduced spontaneous locomotor activity. In contrast, the FAAH inhibitor -2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide) was largely without effect in these assays. Consistent with previous studies showing that combined inhibition of FAAH and MAGL produces a substantially greater cannabimimetic profile than single enzyme inhibition, the dual FAAH-MAGL inhibitor SA-57 (4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester) produced a similar magnitude of ICSS depression as that produced by THC. ICSS attenuation by JZL184 was associated with increased brain levels of 2-arachidonoylglycerol (2-AG), whereas peak effects of SA-57 were associated with increased levels of both N-arachidonoylethanolamine (anandamide) and 2-AG. The cannabinoid receptor type 1 receptor antagonist rimonabant, but not the cannabinoid receptor type 2 receptor antagonist SR144528, blocked the attenuating effects of THC, JZL184, and SA-57 on ICSS. Thus, THC, MAGL inhibition, and dual FAAH-MAGL inhibition not only reduce ICSS, but also decrease other reinforced and nonreinforced behaviors.

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Section: Introductionsupporting

confidence: 78%

Δ⁹-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Wiebelhaus

Grim

Owens

et al. 2014

J Pharmacol Exp Ther

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“…17 Therefore, ⌬9-THC may influence learning and memory by modulating function in these regions. In experimental animals, administration of ⌬9-THC also increases dopaminergic neuronal firing 18 and striatal dopamine release, 19 which has led to the suggestion that induction of psychotic symptoms by C sativa may reflect a secondary effect of ⌬9-THC on striatal dopamine release. 20 Although there is evidence that striatal dopamine activity may mediate acute psychotic symptoms in schizophrenia, 21 an effect of ⌬9-THC on striatal dopamine release has not been demonstrated in humans.…”

Section: Arch Gen Psychiatry 2009;66(4):442-451mentioning

confidence: 99%

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol

Bhattacharyya¹,

Fusar‐Poli²,

Borgwardt³

et al. 2009

Arch Gen Psychiatry

227

132

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“…Mice that were initially trained to perform an operant for food and water reinforcement also intravenously self-administered about 2.0-4.0 mg/kg/day [40][41][42][43] .…”

Section: Acquisition Of Mdma Self-administration In Laboratory Animalsmentioning

confidence: 99%

MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

Schenk

2009

Neuropsychobiology

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The prevalence of 3,4-methylenedioxymethamphetamine (MDMA) use has increased globally and the pattern of consumption has changed considerably. Previously, a subculture of MDMA users was fairly restricted to the dance club scene. More recently, use has spread outside of this subculture and now many users consume MDMA frequently and in large amounts and some meet criteria for drug abuse and/or dependence. Because of confounds associated with studying drug users and abusers, animal models have been employed to investigate potential consequences of drug-taking. Among these, self-administration by laboratory animals has been shown to have excellent predictive validity. There have, however, been mixed results with respect to the ability of MDMA to support and maintain self-administration by laboratory animals. This paper reviews the literature on MDMA self-administration in laboratory primates and rodents. Most of the studies in laboratory animals suggest that only low levels of MDMA are self-administered on a daily basis but some have indicated high levels of self-administered MDMA in certain subjects. Differences might be dependent upon the number of test sessions, prior training conditions or other paradigmatic variables. In most cases, MDMA was found to be a lower efficacy reinforcer than other drugs of abuse. It is suggested that the MDMA self-administration develops following a decrease in MDMA-produced serotonin release that occurs with repeated exposure over an extended period of testing. It is hypothesized that the deficit in central serotonin increases the relative MDMA-produced dopamine responses and that this increase in the dopamine response underlies the development and maintenance of MDMA self-administration.

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Behavioural and neurochemical effects of combined MDMA and THC administration in mice

Abstract: These results demonstrate that a low dose of THC modifies in different ways (increases and decreases) the sensitivity of animals to the behavioural effects of MDMA and that THC and MDMA converge at a common mechanism modulating DA outflow in the NAC of mice.

Cited by 36 publications

References 32 publications

Δ⁹-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Δ⁹-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol

MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

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Behavioural and neurochemical effects of combined MDMA and THC administration in mice

Abstract: These results demonstrate that a low dose of THC modifies in different ways (increases and decreases) the sensitivity of animals to the behavioural effects of MDMA and that THC and MDMA converge at a common mechanism modulating DA outflow in the NAC of mice.

Cited by 36 publications

References 32 publications

Δ9-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Δ9-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol

MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

Contact Info

Product

Resources

About

Δ⁹-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice

Δ⁹-Tetrahydrocannabinol and Endocannabinoid Degradative Enzyme Inhibitors Attenuate Intracranial Self-Stimulation in Mice