Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans
Abstract
Rationale Prepulse inhibition of acoustic startle refers to the reduction in the startle response when the startling stimulus is preceded by a weak prepulse stimulus. This phenomenon provides an operational measure of sensorimotor gating that has been found to be reduced in patients with schizophrenia and rats treated with serotonin agonists or serotonin releasers.Objective In this study, we compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in laboratory rats and healthy human volunteers. In particular, we investigated whether MDMA disrupts PPI in humans as observed in animal studies.Methods Rats were tested after placebo and MDMA in a counterbalanced order at an interval of 1 week, with separate groups of rats being used for each dose of MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after no injections and retested 2 h later, 10 min after a subcutaneous injection of placebo or MDMA. For the human study, a placebo-controlled within-subject design and double-blind procedures were used. Subjects were examined twice at a 2 to 4 week interval after either placebo or drug administration (order being counterbalanced). On each test day, subjects underwent baseline testing including psychological and PPI measures. Ninety minutes later, subjects received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during the peak of behavioral effects of MDMA.Results As expected, MDMA decreased prepulse inhibition in a dose-related fashion in rats. In contrast, a typical recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in subjects experiencing robust psychological effects.Conclusions This surprising disparity between the effects of the drug in rats and humans may reflect a species-specific difference in the mechanism of action of MDMA or in the behavioral expression of a similar pharmacological effect, or both.
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Earlier controlled lab work suggests MDMA raises self-reported states tied to empathy and social ease, but findings are mixed.
“These studies indicate that MDMA increases feelings related to empathy and sociability, including self-rated friendliness [7–8], extroversion [9–10], closeness to others [11], sociability [7, 12], talkativeness [7–8], amicability, and gregariousness [13], although some of these effects are inconsistent [14–16].”
From Is Ecstasy an “Empathogen”? Effects of +/- 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others (2010) · cites this paper as [9]
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- Authors
- Vollenweider, F. X., Remensberger, S., Hell, D., & Geyer, M. A.
- Affiliations
- Psychiatrische Universitätsklinik Zürich (CH)
- University of California San Diego (US)
- Venue
- Psychopharmacology
- Published
- 1999-04-26
- Volume
- 143
- Issue
- 4
- Pages
- 365-372
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W3021847224
- Cited by
- 97
- References
- 30
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 11.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH01228)
- National Institute on Drug Abuse (DA 02925, R01DA002925)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- MDMA, 3,4-methylenedioxymethamphetamine, prepulse inhibition, sensorimotor gating, acoustic startle response, serotonin release, species differences, dose-response relationship, schizophrenia
- MeSH terms
- Acoustic Stimulation, Adult, Affect, Analysis of Variance, Animals, Dose-Response Relationship, Drug, Double-Blind Method, Habituation, Psychophysiologic, Humans, Middle Aged, Psychometrics, Reflex, Startle, Rats, Sprague-Dawley, Serotonin Agents, N-Methyl-3,4-methylenedioxyamphetamine, Rats
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