PMID- 19421742
OWN - NLM
STAT- MEDLINE
DCOM- 20091005
LR  - 20211028
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 205
IP  - 2
DP  - 2009 Aug
TI  - Role of dopamine transporters in the behavioral effects of 
      3,4-methylenedioxymethamphetamine (MDMA) in nonhuman primates.
PG  - 337-47
LID - 10.1007/s00213-009-1545-0 [doi]
AB  - RATIONALE: The interoceptive and reinforcing effects of 
      3,4-methylenedioxymethamphetamine (MDMA) are similar to those of 
      psychostimulants, but the role of dopamine in the behavioral effects of MDMA is 
      not well documented, especially in primates. OBJECTIVE: The aim of this study was 
      to assess the role of dopamine in the behavioral effects of MDMA in two nonhuman 
      primate species. METHODS: The behavioral effects of MDMA, with and without 
      serotonergic or dopaminergic pretreatments, were studied in squirrel monkeys 
      trained to respond under a fixed-interval schedule of stimulus termination; 
      effects on caudate dopamine levels were studied in a separate group of squirrel 
      monkeys using in vivo microdialysis. Positron emission tomography neuroimaging 
      with the dopamine transporter (DAT) ligand [18F]FECNT was used to determine DAT 
      occupancy by MDMA in rhesus monkeys. RESULTS: MDMA (0.5-1.5 mg/kg) did not induce 
      behavioral stimulant effects, but the highest dose of MDMA suppressed responding. 
      Pretreatment with fluoxetine (3.0 mg/kg) or the selective 5HT(2A) antagonist 
      M100907 (0.03-0.3 mg/kg) attenuated the rate suppressing effects of MDMA. In 
      contrast, pretreatment with the selective dopamine transporter inhibitor RTI-177 
      (0.1 mg/kg) did not alter the rate suppressing effects of MDMA. Administration of 
      MDMA at a dose that suppressed operant behavior had negligible effects on 
      extracellular dopamine. The percent DAT occupancy of MDMA at a dose that 
      suppressed operant behavior also was marginal and reflected low in vivo potency 
      for DAT binding. CONCLUSIONS: Collectively, these results indicate that 
      behaviorally relevant doses of MDMA do not induce behavioral stimulant or 
      dopamine transporter-mediated effects in nonhuman primates.
FAU - Fantegrossi, William E
AU  - Fantegrossi WE
AD  - Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock, AR, USA.
FAU - Bauzo, Rayna M
AU  - Bauzo RM
FAU - Manvich, Daniel M
AU  - Manvich DM
FAU - Morales, Jose C
AU  - Morales JC
FAU - Votaw, John R
AU  - Votaw JR
FAU - Goodman, Mark M
AU  - Goodman MM
FAU - Howell, Leonard L
AU  - Howell LL
LA  - eng
GR  - K02 DA000517/DA/NIDA NIH HHS/United States
GR  - Z01 DA000517/ImNIH/Intramural NIH HHS/United States
GR  - RR020146/RR/NCRR NIH HHS/United States
GR  - DA20645/DA/NIDA NIH HHS/United States
GR  - P20 RR020146/RR/NCRR NIH HHS/United States
GR  - P51 RR000165/RR/NCRR NIH HHS/United States
GR  - K02 DA000517-10/DA/NIDA NIH HHS/United States
GR  - R01 DA012514/DA/NIDA NIH HHS/United States
GR  - R01 DA012514-10/DA/NIDA NIH HHS/United States
GR  - RR00165/RR/NCRR NIH HHS/United States
GR  - DA10344/DA/NIDA NIH HHS/United States
GR  - DA12514/DA/NIDA NIH HHS/United States
GR  - R37 DA010344/DA/NIDA NIH HHS/United States
GR  - R01 DA010344/DA/NIDA NIH HHS/United States
GR  - R37 DA010344-13/DA/NIDA NIH HHS/United States
GR  - R21 DA020645/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090507
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (2-carbomethoxy-3-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane)
RN  - 0 (3-(4'-chlorophenyl)-2-(3'-phenylisoxazol-5'-yl)tropane)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Fluorobenzenes)
RN  - 0 (Hallucinogens)
RN  - 0 (Nortropanes)
RN  - 0 (Piperidines)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Tropanes)
RN  - 44RAL3456C (Methamphetamine)
RN  - EW71EE171J (volinanserin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Brain/diagnostic imaging/drug effects
MH  - Central Nervous System Stimulants/pharmacology
MH  - Conditioning, Operant/drug effects/physiology
MH  - Dopamine Plasma Membrane Transport Proteins/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Electrochemical Techniques/methods
MH  - Female
MH  - Fluorine Radioisotopes/metabolism
MH  - Fluorobenzenes/pharmacology
MH  - Hallucinogens/*pharmacology
MH  - Macaca mulatta
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Methamphetamine/pharmacology
MH  - Microdialysis/methods
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Nortropanes/metabolism
MH  - Piperidines/pharmacology
MH  - Positron-Emission Tomography/methods
MH  - Reinforcement Schedule
MH  - Saimiri
MH  - Serotonin Antagonists/pharmacology
MH  - Tropanes/pharmacology
PMC - PMC3230037
MID - NIHMS340202
EDAT- 2009/05/08 09:00
MHDA- 2009/10/06 06:00
PMCR- 2011/12/05
CRDT- 2009/05/08 09:00
PHST- 2008/10/14 00:00 [received]
PHST- 2009/04/11 00:00 [accepted]
PHST- 2009/05/08 09:00 [entrez]
PHST- 2009/05/08 09:00 [pubmed]
PHST- 2009/10/06 06:00 [medline]
PHST- 2011/12/05 00:00 [pmc-release]
AID - 10.1007/s00213-009-1545-0 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2009 Aug;205(2):337-47. doi: 
      10.1007/s00213-009-1545-0. Epub 2009 May 7.