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

Janelle van Wel (1) , Kim Pc Kuypers (1) , Eef L. Theunissen (1) , Wendy Bosker (1) , Katja Bakker (1) , Johannes G Ramaekers (1)

1 Neuropsychology & Psychopharmacology

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-HT2A and 5-HT1A receptors in MDMA induced memory impairment. Ketanserin is a 5-HT2A receptor blocker and pindolol a 5-HT1A 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 6 experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 minutes. T1-T2 combinations were: placebo-placebo, pindolol 20mg-placebo, ketanserin 50mg-placebo, placebo-MDMA 75mg, pindolol 20mg-MDMA 75mg and ketanserin 50mg-MDMA 75 mg. Memory function was assessed at Tmax of MDMA by means of a word learning task, a spatial memory task and a prospective memory task. MDMA significantly impaired performance in all memory tasks. Pretreatment with a 5-HT2A receptor blocker selectively interacted with subsequent MDMA treatment and prevented MDMA induced impairment in the word learning task, but not in the spatial and prospective memory task. Pretreatment with a 5-HT1A 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 word learning task is mediated by 5-HT2A receptor stimulation.

Mots clés: Psychopharmacology; Psychostimulants; Serotonin; Learning & Memory; Receptors

Janelle van Wel, Kim Pc Kuypers, Eef L. Theunissen, Wendy Bosker, Katja Bakker, et al.. Blockade of 5-HT2 receptor selectively prevents MDMA induced verbal memory impairment. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.80⟩. ⟨hal-00640225⟩