title: Blockade of 5-HT2 receptor selectively prevents MDMA-induced verbal memory impairment.
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.
authors.affiliation: Department Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands. Janelle.vanWel@maastrichtuniversity.nl
authors.forename: J H P
authors.initials: JH
authors.lastname: van Wel
authors.forename: K P C
authors.initials: KP
authors.lastname: Kuypers
authors.forename: E L
authors.initials: EL
authors.lastname: Theunissen
authors.forename: W M
authors.initials: WM
authors.lastname: Bosker
authors.forename: K
authors.initials: K
authors.lastname: Bakker
authors.forename: J G
authors.initials: JG
authors.lastname: Ramaekers
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010919:Placebos; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D018490:Serotonin Agents / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D010919:Placebos; D058830:Serotonin 5-HT2 Receptor Antagonists; D018490:Serotonin Agents; D018817:N-Methyl-3,4-methylenedioxyamphetamine