Effects of acute MDMA intoxication on mood and impulsivity: role of the 5-HT2 and 5-HT1 receptors.
MDMA induces positive mood and increases impulse control during intoxication, but only a few studies on the neuropharmacological mechanisms underlying these processes have been conducted. It was hypothesized that pretreatment with 5-HT(1) and 5-HT(2) receptor blockers would prevent MDMA effects on mood and impulsivity. 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, 20 mg pindolol-placebo, 50 mg ketanserin-placebo, placebo-75 mg MDMA, 20 mg pindolol-75 mg MDMA and 50 mg ketanserin-75 g MDMA. Subjects completed a Profile of Mood States (POMS) questionnaire and several impulsivity tasks (Stop signal task, Matching familiar figures task, Cue dependent reversal learning task) at 1.5 hrs post-treatment. MDMA alone increased both positive (vigor, arousal, friendliness, elation, positive mood) and negative affect (anxiety, confusion) as assessed by the POMS questionnaire. MDMA also increased stop reaction time in the Stop signal task and reaction time in the Matching familiar figures task. Pretreatment with ketanserin blocked MDMA effects on positive affect, but not negative affect. Ketanserin did not influence the effects of MDMA on impulsivity. Pindolol did not interact with MDMA on any of the measures. In conclusion, 5-HT(2) receptors mediate positive moods induced by MDMA but not negative moods or impulsivity. 5-HT(1) receptors do not appear to be involved in MDMA effects on mood and impulse control.


BACKGROUND
Nederlands Trial Register NTR2352.
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands. Janelle.vanWel@maastrichtuniversity.nl
Janelle H P
JH
van Wel
Kim P C
KP
Kuypers
Eef L
EL
Theunissen
Wendy M
WM
Bosker
Katja
K
Bakker
Johannes G
JG
Ramaekers
D000328:Adult; D000339:Affect / Q000187:drug effects*; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy* / Q000378:metabolism*; D007858:Learning / Q000187:drug effects; D016014:Linear Models; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D013647:Task Performance and Analysis; D055815:Young Adult
D044263:Receptors, Serotonin, 5-HT1; D044348:Receptors, Serotonin, 5-HT2; D058829:Serotonin 5-HT1 Receptor Antagonists; D018817:N-Methyl-3,4-methylenedioxyamphetamine