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

作者：Nawata Yoko; Hiranita Takato; Yamamoto Tsuneyuki^*

来源：Neuropsychopharmacology, 2010, 35(2): 515-520.

DOI：10.1038/npp.2009.158

• MDMA
• cannabinoid CB1 receptors
• recognition memory
• novel object recognition task
• withdrawal
• hippocampus

(+/-)-3,4-Methylenedioxymethamphetamine (MDMA, 'Ecstasy') abusers have persistent neuropsychiatric deficits including memory impairments after the cessation of abuse. On the other hand, cannabinoid CB1 receptors 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. In this study, we clarified the mechanism underlying the cognitive impairment that develops during MDMA withdrawal from the standpoint of the cannabinoid CB1 receptors. Mice were administered MDMA (10 mg/kg, i.p.) once a day for 7 days. On the 7th day of withdrawal, a novel object recognition task was performed and the amount of cannabinoid CB1 receptor protein was measured with western blotting. Recognition performance was impaired on the 7th day of withdrawal. This impairment was blocked by AM251, a cannabinoid CB1 receptor antagonist, administered 30 min before the training trial or co-administered with MDMA. At this time, the level of cannabinoid CB1 receptor protein increased significantly in the hippocampus but not the prefrontal cortex or striatum. This increase of CB1 receptor protein in the hippocampus was also blocked by the co-administration of AM251. Furthermore, CB1 receptor knockout mice showed no impairment of recognition performance on the withdrawal from MDMA. The impairment of recognition memory during withdrawal from MDMA may result from the activation of cannabinoid CB1 receptors in the hippocampus. Neuropsychopharmacology (2010) 35, 515-520; doi: 10.1038/npp.2009.158; published online 14 October 2009

• 出版日期2010-1