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Blockade of 5-HT2 Receptor Selectively Prevents MDMA-Induced Verbal Memory Impairment

Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen, Wendy M. Bosker, Katja Bakker, Johannes G. Ramaekers

Neuropsychopharmacology May 11, 2011 DOI: 10.1038/npp.2011.80 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled, within-subject design Peer reviewed
Sample size 17
Population Human subjects
Interventions MDMA Ketanserin Pindolol
Dose 75 mg MDMA, 20 mg pindolol, 50 mg ketanserin
Topics MDMA Serotonin
Keywords Blockade Memory impairment Receptor
Citations 52
Key points MDMA-induced impairment of verbal memory is mediated by 5-HT(2A) receptor stimulation.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) or 'ecstasy' has been associated with memory deficits during abstinence and intoxication. The human neuropharmacology of MDMA-induced memory impairment is unknown. This study investigated the role of 5-HT(2A) and 5-HT(1A) receptors in MDMA-induced memory impairment. Ketanserin is a 5-HT(2A) receptor blocker and pindolol a 5-HT(1A) receptor blocker. It was hypothesized that pretreatment with ketanserin and pindolol would protect against MDMA-induced memory impairment. Subjects (N=17) participated in a double-blind, placebo-controlled, within-subject design involving six experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 min. T1-T2 combinations were: placebo-placebo, pindolol 20 mg-placebo, ketanserin 50 mg-placebo, placebo-MDMA 75 mg, pindolol 20 mg-MDMA 75 mg, and ketanserin 50 mg-MDMA 75 mg. Memory function was assessed at Tmax of MDMA by means of a word-learning task (WLT), a spatial memory task and a prospective memory task. MDMA significantly impaired performance in all memory tasks. Pretreatment with a 5-HT(2A) receptor blocker selectively interacted with subsequent MDMA treatment and prevented MDMA-induced impairment in the WLT, but not in the spatial and prospective memory task. Pretreatment with a 5-HT(1A) blocker did not affect MDMA-induced memory impairment in any of the tasks. Together, the results demonstrate that MDMA-induced impairment of verbal memory as measured in the WLT is mediated by 5-HT(2A) receptor stimulation.

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