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)
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 |
| 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.