Prevention of drug priming- and cue-induced reinstatement of MDMA-seeking behaviors by the CB1 cannabinoid receptor antagonist AM251.
Yoko Nawata, Kiyoyuki Kitaichi, Tsuneyuki Yamamoto
Drug and Alcohol Dependence March 1, 2016 DOI: 10.1016/j.drugalcdep.2015.12.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study (rat self-administration and reinstatement) Peer reviewed |
|---|---|
| Population | Rats trained to self-administer MDMA or methamphetamine |
| Interventions | MDMA Methamphetamine AM251 |
| Dose | MDMA 0.3 mg/infusion self-administered; MDMA priming 3.2 mg/kg i.p.; methamphetamine 0.02 mg/infusion self-administered; methamphetamine priming 1.0 mg/kg i.p. |
| Topics | MDMA |
| Keywords | Cb1 cannabinoid receptor Drug-seeking behavior Methamphetamine Self-administration |
| Key points | MDMA priming and MDMA-associated cues reinstated MDMA-seeking in MDMA-trained rats, and methamphetamine priming also reinstated MDMA-seeking, whereas MDMA did not reinstate methamphetamine-seeking in methamphetamine-trained rats. The CB1 antagonist AM251 dose-dependently attenuated MDMA-seeking induced by priming or cues, which the authors propose may support CB1-blocking drugs as a treatment for MDMA dependence. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA), a methamphetamine (METH) derivative, exhibits METH-like actions at monoamine transporters and positive reinforcing effects in rodents and primates. The purposes of the present study were to determine whether cross-reinstatement would be observed between MDMA and METH and if the cannabinoid receptor, a receptor known to play critical roles in the brain reward system, could modulate MDMA craving. Rats were trained to press a lever for intravenous MDMA (0.3mg/infusion) or METH (0.02mg/infusion) infusions under a fixed ratio 1 schedule paired with drug-associated cues (light and tone). Following drug self-administration acquisition training, rats underwent extinction training (an infusion of saline). Reinstatement tests were performed once the extinction criteria were achieved. In MDMA-trained rats, the MDMA-priming injection (3.2mg/kg, i.p.) or re-exposure to MDMA-associated cues reinstated MDMA-seeking behavior. Additionally, a priming injection of METH (1.0mg/kg, i.p.) also reinstated MDMA-seeking behavior. In contrast, none of the MDMA doses reinstated METH-seeking behavior in the METH-trained rats. The CB1 cannabinoid receptor antagonist AM251 markedly attenuated the MDMA-seeking behaviors induced by MDMA-priming injection or re-exposure to MDMA-associated cues in a dose-dependent manner. These findings show that MDMA has obvious addictive potential for reinstating drug-seeking behavior and that METH can be an effective stimulus for reinstating MDMA-seeking behaviors. Furthermore, based on the attenuating effect of AM251 in the reinstatement of MDMA-seeking behaviors, drugs that suppress CB1 receptors may be used in treatment of MDMA dependence.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse Journal of Neurochemistry March 12, 2021
- 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
- Extinction training following cocaine or MDMA self-administration produces discrete changes in D2-like and mGlu5 receptor density in the rat brain. Pharmacological Reports October 2019
Cites 7
- Role of the endocannabinoid system in MDMA intracerebral self‐administration in rats British Journal of Pharmacology August 1, 2002
- Dopaminergic mechanisms of reinstatement of MDMA‐seeking behaviour in rats British Journal of Pharmacology December 30, 2010
- A cannabinoid CB(1) receptor antagonist ameliorates impairment of recognition memory on withdrawal from MDMA (Ecstasy). Neuropsychopharmacology January 2010
- CB1 cannabinoid receptor modulates 3,4-methylenedioxymethamphetamine acute responses and reinforcement. Biological Psychiatry June 1, 2008
- Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity. Psychopharmacology May 2004
and 2 more in the library