PMID- 15039771
OWN - NLM
STAT- MEDLINE
DCOM- 20040802
LR  - 20150311
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 29
IP  - 7
DP  - 2004 Jul
TI  - Behavioral and neurochemical consequences of long-term intravenous 
      self-administration of MDMA and its enantiomers by rhesus monkeys.
PG  - 1270-81
AB  - The effects of self-administered 3,4-methylenedioxymethamphetamine (MDMA) on 
      behavior and neurochemistry have not been previously studied in laboratory 
      primates. We investigated the capacity of MDMA and its enantiomers to maintain 
      contingent responding over an extended duration, whether any decrements in the 
      reinforcing effects of these compounds would be observed over time, whether such 
      decrements would be MDMA-selective, and whether any neurochemical correlates 
      could be identified. Animals were previously trained to self-administer cocaine, 
      then exposed to periodic substitutions of various doses of racemic MDMA and its 
      enantiomers; full dose-effect curves were generated for each MDMA compound 
      repeatedly over the duration of the study. After approximately 18 months of MDMA 
      self-administration, drug exposure was halted and after at least 2 months drug 
      abstinence, animals were scanned using positron emission tomography (PET) with 
      the vesicular monoamine transporter (VMAT) ligand dihydrotetrabenazine (DTBZ). 
      Shortly thereafter, animals were euthanized, brains were dissected, and samples 
      were assayed for brain monoamines and their metabolites using high-performance 
      liquid chromatography (HPLC), and for VMAT using DTBZ binding. The reinforcing 
      effects of racemic and R(-)-MDMA were reduced over a long series (months) of 
      individual self-administration access periods; the reinforcing effects of S+-MDMA 
      were more resistant to this effect, but were attenuated for one animal. The 
      reinforcing effects of cocaine were not altered by chronic MDMA 
      self-administration, nor was the VMAT binding potential as assessed by PET. 
      Further, there were no measurable decrements in serotonin (5-HT), 
      5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic 
      acid (DOPAC) or VMAT in any brain regions assayed. The reinforcing effects of 
      MDMA are selectively attenuated by chronic MDMA self-administration, although 
      this behavioral change appears to occur in the absence of any frank neurochemical 
      correlates of toxicity.
CI  - Copyright 2004 Nature Publishing Group
FAU - Fantegrossi, William E
AU  - Fantegrossi WE
AD  - Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 
      48101-0632, USA. billfan@umich.edu
FAU - Woolverton, William L
AU  - Woolverton WL
FAU - Kilbourn, Michael
AU  - Kilbourn M
FAU - Sherman, Phillip
AU  - Sherman P
FAU - Yuan, Jie
AU  - Yuan J
FAU - Hatzidimitriou, George
AU  - Hatzidimitriou G
FAU - Ricaurte, George A
AU  - Ricaurte GA
FAU - Woods, James H
AU  - Woods JH
FAU - Winger, Gail
AU  - Winger G
LA  - eng
GR  - DA00206/DA/NIDA NIH HHS/United States
GR  - DA05707/DA/NIDA NIH HHS/United States
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, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Serotonin Agents)
RN  - 10028-17-8 (Tritium)
RN  - 3466-75-9 (dihydrotetrabenazine)
RN  - 44RAL3456C (Methamphetamine)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - Z9O08YRN8O (Tetrabenazine)
SB  - IM
CIN - Neuropsychopharmacology. 2004 Oct;29(10):1940-1; author reply 1942. PMID: 
      15383828
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Biogenic Monoamines/metabolism
MH  - Brain/blood supply/*drug effects
MH  - Brain Chemistry/*drug effects
MH  - Brain Mapping
MH  - Central Nervous System Stimulants/administration & dosage
MH  - Chromatography, High Pressure Liquid/methods
MH  - Cocaine/pharmacology
MH  - Dopamine Uptake Inhibitors/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Electrochemistry/methods
MH  - Infusions, Intravenous/methods
MH  - Macaca mulatta
MH  - Methamphetamine/administration & dosage
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/chemistry
MH  - ROC Curve
MH  - Radioligand Assay/methods
MH  - Self Administration/methods
MH  - Serotonin Agents/*administration & dosage/chemistry
MH  - Stereoisomerism
MH  - Tetrabenazine/*analogs & derivatives/pharmacokinetics
MH  - Tissue Distribution
MH  - Tomography, Emission-Computed/methods
MH  - Tritium/pharmacokinetics
EDAT- 2004/03/25 05:00
MHDA- 2004/08/03 05:00
CRDT- 2004/03/25 05:00
PHST- 2004/03/25 05:00 [pubmed]
PHST- 2004/08/03 05:00 [medline]
PHST- 2004/03/25 05:00 [entrez]
AID - 1300442 [pii]
AID - 10.1038/sj.npp.1300442 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2004 Jul;29(7):1270-81. doi: 10.1038/sj.npp.1300442.