PMID- 20477756
OWN - NLM
STAT- MEDLINE
DCOM- 20101102
LR  - 20161125
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Linking)
VI  - 15
IP  - 3
DP  - 2010 Jul
TI  - Tolerance to 3,4-methylenedioxymethamphetamine is associated with impaired 
      serotonin release.
PG  - 289-98
LID - 10.1111/j.1369-1600.2010.00217.x [doi]
AB  - Tolerance to the behavioural effects of 3,4-methylenedioxymethamphetamine (MDMA) 
      following high dose exposure has been attributed to alterations in serotonergic 
      systems. The present study aimed to determine whether decreased 5-HT release 
      and/or 5-HT(2A/C) receptor desensitization might play a role in tolerance by 
      measuring the response to selective ligands following MDMA exposure. To this end, 
      the latency to nose poke and emerge from a hide box to an open field arena 
      following administration of various ligands to MDMA pre-treated and control rats 
      was measured. Acute exposure to MDMA (0.0-3.3 mg/kg), the 5-HT releasing 
      stimulant fenfluramine (0.0-2.0 mg/kg) and the 5-HT(2) receptor agonist m-CPP 
      (0.0-1.25 mg/kg) increased nose poke and emergence latency. Following 
      administration of doses that produce 5-HT(2A) receptor-mediated behaviours, the 
      5-HT(2) receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane 
      failed to alter nose poke and emergence latency, suggesting a limited role of 
      this receptor subtype in these behaviours. Activation of 5-HT(2C) receptors was 
      implicated in the behavioural response to both MDMA and m-CPP since the increased 
      emergence latency was dose-dependently attenuated by pre-treatment with the 
      selective 5-HT(2C) receptor antagonist RS102221 (0.0-1.0 mg/kg). Tolerance to the 
      behavioural effect of MDMA and fenfluramine but not m-CPP was produced by prior 
      exposure to MDMA (10 mg/kg administered at two-hour intervals, total 40 mg/kg), 
      and tissue levels of 5-HT and 5-HIAA were decreased. These findings suggest that 
      tolerance to the increased nose poke and emergence latency produced by MDMA is 
      due to impaired 5-HT release.
FAU - Jones, Karen
AU  - Jones K
AD  - School of Psychology, Victoria University of Wellington, New Zealand.
FAU - Brennan, Katharine A
AU  - Brennan KA
FAU - Colussi-Mas, Joyce
AU  - Colussi-Mas J
FAU - Schenk, Susan
AU  - Schenk S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100511
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (Amphetamines)
RN  - 0 (Piperazines)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptor, Serotonin, 5-HT2C)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 2DS058H2CF (Fenfluramine)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
RN  - REY0CNO998 (1-(3-chlorophenyl)piperazine)
SB  - IM
MH  - Amphetamines/pharmacology
MH  - Animals
MH  - Brain/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Tolerance
MH  - Exploratory Behavior/drug effects
MH  - Fenfluramine/pharmacology
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Piperazines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reaction Time/drug effects
MH  - Receptor, Serotonin, 5-HT2A/drug effects
MH  - Receptor, Serotonin, 5-HT2C/*drug effects
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*pharmacology
MH  - Serotonin Receptor Agonists/pharmacology
EDAT- 2010/05/19 06:00
MHDA- 2010/11/03 06:00
CRDT- 2010/05/19 06:00
PHST- 2010/05/19 06:00 [entrez]
PHST- 2010/05/19 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
AID - ADB217 [pii]
AID - 10.1111/j.1369-1600.2010.00217.x [doi]
PST - ppublish
SO  - Addict Biol. 2010 Jul;15(3):289-98. doi: 10.1111/j.1369-1600.2010.00217.x. Epub 
      2010 May 11.