Effects of MDMA (Ecstasy) on Prepulse Inhibition and Habituation of Startle in Humans after Pretreatment with Citalopram, Haloperidol, or Ketanserin

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 24; no. 3; pp. 240 - 252
• Main Authors: Liechti, Matthias E, Geyer, Mark A, Hell, Daniel, Vollenweider, Franz X
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-03-2001; Nature Publishing; Nature Publishing Group
• Subjects: 3,4-Methylenedioxy-N-methylamphetamine; Acoustic Stimulation; Adult; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Citalopram; Citalopram - pharmacology; Citalopram - therapeutic use; Dopamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug addictions; Ecstasy; Female; Habituation; Habituation, Psychophysiologic - drug effects; Haloperidol; Haloperidol - pharmacology; Human; Humans; Ketanserin; Ketanserin - pharmacology; Male; MDMA; Medical sciences; Models, Psychological; N-Methyl-3,4-methylenedioxyamphetamine - administration & dosage; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Prepulse inhibition; Psychiatric Status Rating Scales - standards; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Reflex, Startle - drug effects; Reflex, Startle - physiology; Schizophrenia; Serotonin; Serotonin - metabolism; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; Startle; Toxicology; Switzerland; Ecstasy; Human; Serotonin; 3,4-Methylenedioxy-N-methylamphetamine; Startle; Haloperidol; MDMA; Citalopram; Ketanserin; Prepulse inhibition; Habituation; Intravenous administration; Psychotropic; Toxicity; Schizophrenia; Startle reflex; Reuptake inhibitor; Psychosis; Prevention; Acoustic stimulus; Antagonist; Inhibition; Mechanism of action; Drug addiction; Healthy subject; CNS stimulant; Illicit drug; Oral administration; Butyrophenone derivatives; 5-HT2 Serotonine receptor; Chemotherapy; D2 Dopamine receptor
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(00)00199-8

Prepulse inhibition (PPI) of the acoustic startle response is an operational measure of sensorimotor gating that can be assessed in animals and in humans. Serotonin releasers such as MDMA disrupt PPI and reduce startle habituation in rodents. These effects are prevented by pretreatment with selective serotonin uptake inhibitors, indicating that the effect of MDMA on startle plasticity is largely due to carrier-mediated release of serotonin from presynaptic terminals. In contrast, MDMA has been shown to increase PPI in humans. It is unclear, however, whether the MDMA-induced increase in PPI in humans is also dependent on carrier-mediated serotonin release and which postsynaptic receptors are involved. We investigated the effects of three different pretreatments on the MDMA-induced effects on PPI and habituation in humans. Pretreatments were: (1) the highly selective serotonin uptake inhibitor citalopram (40 mg IV) in 16 subjects, (2) the D2 antagonist haloperidol (1.4 mg IV) in 14 subjects, and (3) the 5-HT2A/C antagonist ketanserin (50 mg PO) in 14 subjects. Each of the three studies used a double-blind placebo-controlled design. All healthy volunteers were examined four times at 2–4-week intervals after placebo, pretreatment, MDMA (1.5 mg/kg PO), and pretreatment plus MDMA. MDMA increased PPI. Habituation was not altered by MDMA, although MDMA-induced individual differences on habituation and psychological symptoms were inversely correlated. Citalopram attenuated the MDMA-induced increase in PPI and most of the psychological effects of MDMA. Neither haloperidol nor ketanserin had any effect on PPI increases produced by MDMA, although each partially attenuated some MDMA-induced psychological effects. Results are consistent with the view that MDMA increases PPI of the acoustic startle reflex in humans via release of presynaptic serotonin.