Prevention of drug priming- and cue-induced reinstatement of MDMA-seeking behaviors by the CB1 cannabinoid receptor antagonist AM251. (1st March 2016)

• Record Type: Journal Article
• Authors: Nawata, Yoko; Kitaichi, Kiyoyuki; Yamamoto, Tsuneyuki
• Is Part Of: Drug and alcohol dependence. Volume 160(2016)
• Page Start: 76
• Page End: 81
• Publication Date: 2016-03-01
• Subjects: MDMA -- Methamphetamine -- CB1 cannabinoid receptor -- Drug-seeking behavior -- Self-administration; Drug abuse -- Periodicals; Alcoholism -- Periodicals; 616.86
• DOI: 10.1016/j.drugalcdep.2015.12.016
• Languages: English
• ISSNs: 0376-8716

Abstract

Highlights: MDMA has obvious addictive potential for reinstating drug-seeking behavior. Methamphetamine can be an effective stimulus for reinstating MDMA-seeking behaviors. The CB1 cannabinoid receptor antagonist AM251 markedly blocked the MDMA-seeking behaviors. Drugs that suppress the cannabinoid system via CB1 receptors are expected to treat MDMA dependence. Abstract: Background: 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. Methods: Rats were trained to press a lever for intravenous MDMA (0.3 mg/infusion) or METH (0.02 mg/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. Results: In MDMA-trained rats, the MDMA-priming injection (3.2 mg/kg, i.p.) or re-exposure to MDMA-associated cues reinstated MDMA-seeking behavior. Additionally, a priming injection of METH (1.0 mg/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. Conclusions: 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.