PMID- 15665862
OWN - NLM
STAT- MEDLINE
DCOM- 20050531
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 144
IP  - 2
DP  - 2005 Jan
TI  - A comparative study on the acute and long-term effects of MDMA and 
      3,4-dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or 
      striatal administration in mice.
PG  - 231-41
AB  - 1. This study investigated whether the immediate and long-term effects of 
      3,4-methylenedioxymethamphetamine (MDMA) on monoamines in mouse brain are due to 
      the parent compound and the possible contribution of a major reactive metabolite, 
      3,4-dihydroxymethamphetamine (HHMA), to these changes. The acute effect of each 
      compound on rectal temperature was also determined. 2. MDMA given i.p. (30 mg 
      kg(-1), three times at 3-h intervals), but not into the striatum (1, 10 and 100 
      microg, three times at 3-h intervals), produced a reduction in striatal dopamine 
      content and modest 5-HT reduction 1 h after the last dose. MDMA does not 
      therefore appear to be responsible for the acute monoamine release that follows 
      its peripheral injection. 3. HHMA does not contribute to the acute MDMA-induced 
      dopamine depletion as the acute central effects of MDMA and HHMA differed 
      following i.p. injection. Both compounds induced hyperthermia, confirming that 
      the acute dopamine depletion is not responsible for the temperature changes. 4. 
      Peripheral administration of MDMA produced dopamine depletion 7 days later. 
      Intrastriatal MDMA administration only produced a long-term loss of dopamine at 
      much higher concentrations than those reached after the i.p. dose and therefore 
      bears little relevance to the neurotoxicity. This indicates that the long-term 
      effect is not attributable to the parent compound. HHMA also appeared not to be 
      responsible as i.p. administration failed to alter the striatal dopamine 
      concentration 7 days later. 5. HHMA was detected in plasma, but not in brain, 
      following MDMA (i.p.), but it can cross the blood-brain barrier as it was 
      detected in the brain following its peripheral injection. 6. The fact that the 
      acute changes induced by i.p. or intrastriatal HHMA administration differed 
      indicates that HHMA is metabolised to other compounds which are responsible for 
      changes observed after i.p. administration.
FAU - Escobedo, Isabel
AU  - Escobedo I
AD  - Departamento Farmacologia, Facultad Medicina, Universidad Complutense, 28040 
      Madrid, Spain.
FAU - O'Shea, Esther
AU  - O'Shea E
FAU - Orio, Laura
AU  - Orio L
FAU - Sanchez, Veronica
AU  - Sanchez V
FAU - Segura, Mireia
AU  - Segura M
FAU - de la Torre, Rafael
AU  - de la Torre R
FAU - Farre, Magi
AU  - Farre M
FAU - Green, Alfred Richard
AU  - Green AR
FAU - Colado, Maria Isabel
AU  - Colado MI
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Biogenic Monoamines)
RN  - 15398-87-5 (alpha-methylepinine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7339QLN1C (Deoxyepinephrine)
SB  - IM
MH  - Animals
MH  - Biogenic Monoamines/*metabolism
MH  - Brain/drug effects/metabolism
MH  - Corpus Striatum/*drug effects/metabolism
MH  - Deoxyepinephrine/*administration & dosage/*analogs & derivatives/chemistry
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Injections, Intraperitoneal
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage/chemistry
MH  - Time Factors
PMC - PMC1575997
EDAT- 2005/01/25 09:00
MHDA- 2005/06/01 09:00
PMCR- 2006/01/01
CRDT- 2005/01/25 09:00
PHST- 2005/01/25 09:00 [pubmed]
PHST- 2005/06/01 09:00 [medline]
PHST- 2005/01/25 09:00 [entrez]
PHST- 2006/01/01 00:00 [pmc-release]
AID - sj.bjp.0706071 [pii]
AID - 10.1038/sj.bjp.0706071 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2005 Jan;144(2):231-41. doi: 10.1038/sj.bjp.0706071.