PMID- 16510482
OWN - NLM
STAT- MEDLINE
DCOM- 20060809
LR  - 20221207
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 20
IP  - 2
DP  - 2006 Mar
TI  - Studies on striatal neurotoxicity caused by the 
      3,4-methylenedioxymethamphetamine/ malonate combination: implications for 
      serotonin/dopamine interactions.
PG  - 245-56
AB  - The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) produces 
      long-term toxicity to serotonin (5-HT) neurones in rats, which is exacerbated 
      when combined with the mitochondrial inhibitor malonate. Moreover, MDMA, which 
      does not produce dopamine depletion in the rat, potentiates malonate-induced 
      striatal dopamine toxicity. Because the malonate/MDMA combination acutely causes 
      a synergistic increase of 5-HT and dopamine release, in this study we sought to 
      determine whether pharmacological blockade of MDMA- and/or malonate-induced 
      dopamine release prevents neurotoxicity. Fluoxetine, given 30 min prior to the 
      malonate/MDMA combination, afforded complete protection against 5-HT depletion 
      and reversed MDMA-induced exacerbation of dopamine toxicity found in the 
      malonate/MDMA treated rats. Protection afforded by fluoxetine was not related to 
      changes in MDMA-induced hyperthermia. Similarly, potentiation of malonate-induced 
      dopamine toxicity caused by MDMA was not observed in p-chlorophenylalanine-5-HT 
      depleted rats. Finally, the dopamine transporter inhibitor GBR 12909 completely 
      prevented dopamine neurotoxicity caused by the malonate/MDMA combination and 
      reversed the exacerbating toxic effects of malonate on MDMA-induced 5-HT 
      depletion without significantly altering the hyperthermic response. Overall, 
      these results suggest that the synergic release of dopamine caused by the 
      malonate/MDMA combination plays an important role in the long-term toxic effects. 
      A possible mechanism of neurotoxicity and protection is proposed.
FAU - Goni-Allo, Beatriz
AU  - Goni-Allo B
AD  - Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, 
      Spain.
FAU - Ramos, Mar'a
AU  - Ramos M
FAU - Herv'as, Isabel
AU  - Herv'as I
FAU - Lasheras, Berta
AU  - Lasheras B
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Hallucinogens)
RN  - 0 (Malonates)
RN  - 0 (Piperazines)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 90X28IKH43 (vanoxerine)
RN  - 9KX7ZMG0MK (malonic acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Amphetamine-Related Disorders/*physiopathology
MH  - Animals
MH  - Body Temperature Regulation/drug effects
MH  - Cell Survival/drug effects
MH  - Corpus Striatum/*drug effects/physiopathology
MH  - Dopamine/metabolism
MH  - Dopamine Uptake Inhibitors/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Fluoxetine/pharmacology
MH  - Hallucinogens/*toxicity
MH  - Male
MH  - Malonates/*toxicity
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurons/drug effects
MH  - Piperazines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/metabolism
MH  - Serotonin Agents/*toxicity
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
EDAT- 2006/03/03 09:00
MHDA- 2006/08/10 09:00
CRDT- 2006/03/03 09:00
PHST- 2006/03/03 09:00 [pubmed]
PHST- 2006/08/10 09:00 [medline]
PHST- 2006/03/03 09:00 [entrez]
AID - 20/2/245 [pii]
AID - 10.1177/0269881106063264 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2006 Mar;20(2):245-56. doi: 10.1177/0269881106063264.