PMID- 18824064
OWN - NLM
STAT- MEDLINE
DCOM- 20090415
LR  - 20221207
IS  - 0278-5846 (Print)
IS  - 0278-5846 (Linking)
VI  - 32
IP  - 8
DP  - 2008 Dec 12
TI  - Reduced efficacy of fluoxetine following MDMA ("Ecstasy")-induced serotonin loss 
      in rats.
PG  - 1894-901
LID - 10.1016/j.pnpbp.2008.09.008 [doi]
AB  - Long-term serotonin (5-HT) neuronal loss is currently a major cause of concern 
      associated with recreational use of the substituted amphetamine 3,4 
      methylenedioxymethamphetamine (MDMA; "Ecstasy"). Such loss may be problematic 
      considering that psychiatric disorders such as depression and anxiety and 
      responses to first line treatments for these disorders are associated with 5-HT. 
      In this study the effects of prior exposure to MDMA on behavioural and central 
      neurochemical changes induced by the serotonin (5-HT) re-uptake inhibitor and 
      antidepressant fluoxetine were examined in rats. Animals were administered MDMA 
      (10 mg/kg. i.p.) four times daily for two consecutive days. One week later the 
      animals were subjected to treatment with fluoxetine (10 mg/kg, i.p.). Fluoxetine 
      treatment groups received either acute (saline injections for 20 days followed by 
      3 fluoxetine treatments over 24 h) or chronic (once daily fluoxetine for 21 days) 
      drug administration. Prior exposure to MDMA resulted in an attenuation of 
      fluoxetine-induced swimming behaviour in the modified forced swimming test (FST); 
      a behavioural test of antidepressant action. In parallel MDMA treatment resulted 
      in significant regional depletions of 5-HT and its metabolite 
      5-hydroxyindoleacetic acid (5-HIAA) accompanied by a reduction in cortical [3H] 
      paroxetine binding to nerve terminal 5-HT transporters. MDMA-induced 5-HT loss 
      was enhanced in animals following chronic fluoxetine administration. Elimination 
      of fluoxetine and its metabolite norfluoxetine from the brain abolished this 
      interaction between MDMA and fluoxetine treatment. Fluoxetine administration 
      reduced both 5-HIAA and the 5-HIAA:5-HT metabolism ratio, which was attenuated in 
      animals pre-treated with MDMA. Overall the results show that MDMA induces 
      long-term 5-HT loss in the rodent brain and consequently diminishes behaviour and 
      reductions in 5-HT metabolism induced by the antidepressant fluoxetine. These 
      results have potential clinical relevance, suggesting that 5-HT re-uptake 
      inhibitors such as fluoxetine may be less effective at treating depression in 
      chronic abusers of MDMA.
FAU - Durkin, Sarah
AU  - Durkin S
AD  - Trinity College Institute of Neuroscience, School of Pharmacy and Pharmaceutical 
      Sciences, Trinity College, Dublin 2, Ireland.
FAU - Prendergast, Alison
AU  - Prendergast A
FAU - Harkin, Andrew
AU  - Harkin A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080913
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Hallucinogens)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - 41VRH5220H (Paroxetine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain Chemistry/*drug effects
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Drug Interactions
MH  - Fluoxetine/*pharmacology
MH  - Hallucinogens/*pharmacology
MH  - Immobility Response, Tonic/drug effects
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Paroxetine/pharmacokinetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Selective Serotonin Reuptake Inhibitors/*pharmacology
MH  - Swimming
MH  - Time Factors
MH  - Tritium/pharmacokinetics
EDAT- 2008/10/01 09:00
MHDA- 2009/04/16 09:00
CRDT- 2008/10/01 09:00
PHST- 2008/06/20 00:00 [received]
PHST- 2008/09/03 00:00 [revised]
PHST- 2008/09/03 00:00 [accepted]
PHST- 2008/10/01 09:00 [pubmed]
PHST- 2009/04/16 09:00 [medline]
PHST- 2008/10/01 09:00 [entrez]
AID - S0278-5846(08)00279-0 [pii]
AID - 10.1016/j.pnpbp.2008.09.008 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1894-901. doi: 
      10.1016/j.pnpbp.2008.09.008. Epub 2008 Sep 13.