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Controlled Clinical Trial
. 2011 Aug;36(9):1932-9.
doi: 10.1038/npp.2011.80. Epub 2011 May 11.

Blockade of 5-HT2 receptor selectively prevents MDMA-induced verbal memory impairment

J H P van Wel  1 , K P C Kuypers, E L Theunissen, W M Bosker, K Bakker, J G Ramaekers
Affiliations
Controlled Clinical Trial

Blockade of 5-HT2 receptor selectively prevents MDMA-induced verbal memory impairment

J H P van Wel et al. Neuropsychopharmacology. 2011 Aug.

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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Figures

Figure 1
Figure 1
Mean (SE) immediate recall and prospective memory recall in the word-learning task and the prospective memory task for every treatment condition. Each treatment condition consisted of a pre-treatment (T1) and a treatment (T2). (PLA, placebo; PIN, pindolol; KET, ketanserin; MDMA, 3,4-methylenedioxymethamphetamine, *p<0.05 as indicated by drug-placebo contrasts following a significant main interaction effect of MDMA × ketanserin in the Word-learning task).
Figure 2
Figure 2
Mean (SE) localization error and reaction time in the spatial memory task for every treatment condition. Each treatment condition consisted of a pre-treatment (T1) and a treatment (T2). (PLA, placebo; PIN, pindolol; KET, ketanserin; MDMA, 3,4-methylenedioxymethamphetamine).
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