PMID- 10367553
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20190726
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 143
IP  - 4
DP  - 1999 Apr
TI  - Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor 
      gating in rats versus healthy humans.
PG  - 365-72
AB  - 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.
FAU - Vollenweider, F X
AU  - Vollenweider FX
AD  - Psychiatric University Hospital Zurich, Research Department, Switzerland. 
      vollen@bli.unizh.ch
FAU - Remensberger, S
AU  - Remensberger S
FAU - Hell, D
AU  - Hell D
FAU - Geyer, M A
AU  - Geyer MA
LA  - eng
GR  - DA02925/DA/NIDA NIH HHS/United States
GR  - MH01228/MH/NIMH NIH HHS/United States
PT  - Clinical Trial
PT  - Comparative Study
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Serotonin Agents)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Acoustic Stimulation
MH  - Adult
MH  - Affect/drug effects
MH  - Analysis of Variance
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Habituation, Psychophysiologic/*drug effects
MH  - Humans
MH  - Middle Aged
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology
MH  - Psychometrics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reflex, Startle/*drug effects
MH  - Serotonin Agents/administration & dosage/*pharmacology
EDAT- 1999/06/15 00:00
MHDA- 1999/06/15 00:01
CRDT- 1999/06/15 00:00
PHST- 1999/06/15 00:00 [pubmed]
PHST- 1999/06/15 00:01 [medline]
PHST- 1999/06/15 00:00 [entrez]
AID - 10.1007/s002130050960 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 1999 Apr;143(4):365-72. doi: 10.1007/s002130050960.