PMID- 15983787
OWN - NLM
STAT- MEDLINE
DCOM- 20060215
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 181
IP  - 3
DP  - 2005 Sep
TI  - Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and 
      its enantiomers in the mouse.
PG  - 529-36
AB  - RATIONALE: Drug challenges in "intact" and p-chlorophenylalanine (p-CPA)-treated 
      animals can be used to distinguish agents that act as direct serotonin (5-HT) 
      agonists from agents that function as 5-HT releasers. OBJECTIVES: The objective 
      of the study was to investigate the effect of p-CPA treatment on the capacity of 
      racemic 3,4-methylenedioxymethamphetamine (MDMA) and its stereoisomers to induce 
      the head twitch response, hyperthermia, and locomotor stimulation in mice. 
      METHODS: Pretreatments with either 100 mg/kg p-CPA or equivolume saline were 
      administered for three consecutive days. The following day, mice were either 
      euthanized (to quantify 5-HT tone), tested with various doses of racemic MDMA or 
      one of its enantiomers in the head twitch assay, or challenged with 32 mg/kg 
      racemic MDMA or one of its enantiomers, while temperature and locomotor activity 
      were monitored via radiotelemetry. RESULTS: p-CPA reduced cortical 5-HT turnover 
      by >70% without altering dopamine turnover. Racemic MDMA did not induce a 
      significant head twitch response in intact or p-CPA-treated mice. S(+)-MDMA and 
      R(-)-MDMA elicited similar head twitch curves in intact mice; p-CPA treatment 
      attenuated this response when induced by S(+)-MDMA but not when elicited by 
      R(-)-MDMA. Neither the hyperthermic nor locomotor-stimulant effects of racemic 
      MDMA were altered by p-CPA treatment. The hyperthermic effects, but not the 
      locomotor-stimulant effects, of S(+)-MDMA were attenuated in mice treated with 
      p-CPA. R(-)-MDMA did not alter core temperature or induce significant locomotor 
      stimulation in intact or p-CPA-treated mice. CONCLUSIONS: The effects of 
      S(+)-MDMA on core temperature and head twitch behavior are consistent with a 
      mechanism involving 5-HT release, whereas the effects of R(-)-MDMA on head twitch 
      behavior are consistent with a direct agonist mechanism of action. The actions of 
      the racemate on core temperature and locomotor activity likely involve a 
      combination of 5-HT release and direct agonism at 5-HT receptors.
FAU - Fantegrossi, William E
AU  - Fantegrossi WE
AD  - Division of Neuroscience, Yerkes National Primate Research Center, Emory 
      University, 954 Gatewood Drive, Atlanta, GA 30322, USA. wfanteg@emory.edu
FAU - Kiessel, Christina L
AU  - Kiessel CL
FAU - De la Garza, Richard 2nd
AU  - De la Garza R 2nd
FAU - Woods, James H
AU  - Woods JH
LA  - eng
GR  - DA05923/DA/NIDA NIH HHS/United States
GR  - DA09161/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20051012
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 5.1.- (Racemases and Epimerases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R5J7E3L9SP (Fenclonine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Body Temperature Regulation/*drug effects
MH  - Cerebral Cortex/drug effects
MH  - Dopamine/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fenclonine/*pharmacology
MH  - Locomotion/*drug effects
MH  - Male
MH  - Mice
MH  - Motor Activity/*drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Premedication
MH  - Racemases and Epimerases
MH  - Serotonin/*metabolism
MH  - Serotonin Antagonists/*pharmacology
MH  - Serotonin Receptor Agonists/*pharmacology
MH  - Stereoisomerism
EDAT- 2005/06/29 09:00
MHDA- 2006/02/16 09:00
CRDT- 2005/06/29 09:00
PHST- 2004/11/27 00:00 [received]
PHST- 2005/03/15 00:00 [accepted]
PHST- 2005/06/29 09:00 [pubmed]
PHST- 2006/02/16 09:00 [medline]
PHST- 2005/06/29 09:00 [entrez]
AID - 10.1007/s00213-005-0005-8 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2005 Sep;181(3):529-36. doi: 
      10.1007/s00213-005-0005-8. Epub 2005 Oct 12.