Psychopharmacology (2004) 173:418–424 DOI 10.1007/s00213-003-1729-y ORIGINAL INVESTIGATION Karsten Heekeren · Jörg Daumann · Mark A. Geyer · Euphrosyne Gouzoulis-Mayfrank Plasticity of the acoustic startle reflex in currently abstinent ecstasy (MDMA) users Received: 11 September 2003 / Accepted: 18 November 2003 / Published online: 14 January 2004  Springer-Verlag 2004 Abstract Rationale: 3,4-Methylenedioxymethamphet- amine (MDMA, ecstasy) is neurotoxic upon central serotonin systems in experimental animals and probably also in humans. Serotonin is involved in the habituation, sensitization and prepulse inhibition (PPI) of the startle reflex. Objectives: To study the plasticity of startle reflex in currently abstinent MDMA users. Methods: Electro- myographic responses to acoustic startle stimuli (pulse alone and prepulse-pulse trials) were recorded in 23 currently abstinent ecstasy users and 20 matched control subjects. Depending on the extent of their previous drug use ecstasy users were divided into two groups [life-time dose <90 (n=11) and 90 pills (n=12), respectively]. Results: There were no significant differences in habitu- ation, sensitization or PPI of the startle reflex between the entire group of ecstasy users and controls. However, sensitization of the startle reflex was stronger in the 90 compared with either the <90 MDMA pills or the control group. Correlations between patterns of drug use and startle parameters did not reach the level of significance, although users with a younger age at the onset of MDMA (and other drug) use tended to present with higher sensitization of the startle reflex. Conclusions: Heavy users of MDMA (and other recreational drugs) present with strong sensitization of the startle reflex. Neverthe- less, it is unclear whether this finding is secondary to the use of MDMA and its well-recognized neurotoxic poten- tial. Alternatively, strong sensitization might reflect a pre- existing trait predisposing to drug use. A clearer picture of the impact of ecstasy on startle plasticity may be obtained from longitudinal investigations. Keywords MDMA (3,4-methylenedioxymeth- amphetamine) · Startle reflex · Neurotoxicity · Sensitization · Habituation · Prepulse Inhibition Introduction Ecstasy (MDMA: 3,4-methylenedioxymethamphetamine and other congeners) is a popular recreational drug with well recognized neurotoxic potential upon central seroto- nergic systems (Ricaurte et al. 1992, 2000). Ecstasy use leads to widespread degeneration of presynaptic seroto- nergic axon terminals and serotonin depletion in brain tissue. These effects can be very long-lasting or even permanent in animal studies (Fischer et al. 1995; Hatzidimitriou et al. 1999), and may also occur in humans (McCann et al. 1998, 2000; Reneman et al. 2001). Serotonin is involved in numerous functions, including regulation of mood, vegetative functions, neuroendocrine secretion, processing of sensory stimuli and cognition. Several reports suggest that ecstasy users exhibit abnor- malities in most of these functional domains (reviews in McCann et al. 2000; Gouzoulis-Mayfrank et al. 2002). To date, the most consistent findings have been dose-related impairments of learning and memory performance (Krys- tal et al. 1992; Bolla et al. 1998; Parrott and Lasky 1998; Morgan 1999; Gouzoulis-Mayfrank et al. 2000, 2003; Rodgers 2000; Bhattachary and Powell 2001; Zakzanis and Young 2001; Daumann et al. 2003). With regard to sensory processing, findings have been inconsistent, with one study reporting an association of the extent of previous ecstasy use with the intensity dependence of acoustic evoked potentials and another study reporting an increase of intensity dependence per se but no association with the extent of previous ecstasy use K. Heekeren Department of Psychiatry and Psychotherapy, University of Technology (RWTH), Pauwelsstrasse 30, 52074 Aachen, Germany M. A. Geyer Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA J. Daumann · E. Gouzoulis-Mayfrank ( ) ) Department of Psychiatry and Psychotherapy, University of Cologne, Joseph-Stelzmann Strasse 9, 50924 Cologne, Germany e-mail: e.gouzoulis@uni-koeln.de Tel.: +49-221-4784001 Fax: +49-221-4783738