PMID- 21712712
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20131121
IS  - 1473-5849 (Electronic)
IS  - 0955-8810 (Linking)
VI  - 22
IP  - 4
DP  - 2011 Aug
TI  - Sensitization to MDMA locomotor effects and changes in the functionality of 
      5-HT(2A) and D(2) receptors in mice.
PG  - 362-9
LID - 10.1097/FBP.0b013e3283487346 [doi]
AB  - The behavioral and neurochemical adaptations related to chronic 
      3,4-methylenedioxymethamphetamine (MDMA) treatment are largely unknown. In this 
      study, we assessed whether repeated administration of MDMA would induce (a) 
      context-dependent locomotor sensitization in mice and (b) changes in serotonin 
      5-HT(2A) and dopamine D(2) receptor functionality as measured by [(3)(5)S]GTPgammaS 
      binding. Mice were treated with MDMA (10 mg/kg, intraperitoneally) or saline 
      every other day for 11 days either in their home cages or in the environment 
      where locomotor activity was measured. After a 10-day withdrawal period, mice 
      were challenged with MDMA (5 and 10 mg/kg) and saline before locomotor activity 
      measurements. During repeated MDMA treatment, locomotion was progressively 
      enhanced, indicating the development of behavioral sensitization. The MDMA 
      challenge at a dose of 5 mg/kg increased locomotor activity to a greater extent 
      in mice pretreated with MDMA in the testing apparatus than in mice pretreated in 
      the home cages, revealing that contextual cues paired with repeated drug exposure 
      can enhance the expression of behavioral sensitization to MDMA. In contrast, a 
      challenge administration of MDMA at 10 mg/kg induced similar locomotor 
      sensitization in mice pretreated in both environments. An increase in the 
      functionality of cortical 5-HT(2A) receptors was observed in mice pretreated with 
      MDMA compared with mice pretreated with saline, but this activation was 
      significantly greater in mice pretreated in the locomotor environment. In 
      contrast, the functional activity of striatal D(2) receptors was significantly 
      decreased only in mice pretreated with MDMA in the testing apparatus. These 
      results reveal neuroadaptations in cortical 5-HT(2A) and striatal D(2) receptors 
      after MDMA-induced behavioral sensitization in mice.
FAU - Varela, Maria Jose
AU  - Varela MJ
AD  - Universitat Pompeu Fabra, PRBB, Barcelona, Spain.
FAU - Brea, Jose
AU  - Brea J
FAU - Loza, Maria Isabel
AU  - Loza MI
FAU - Maldonado, Rafael
AU  - Maldonado R
FAU - Robledo, Patricia
AU  - Robledo P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Behav Pharmacol
JT  - Behavioural pharmacology
JID - 9013016
RN  - 0 (Hallucinogens)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Serotonin Agents)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Corpus Striatum/drug effects/metabolism
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Hallucinogens/*pharmacology
MH  - Male
MH  - Mice
MH  - Motor Activity/*drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Receptor, Serotonin, 5-HT2A/*drug effects
MH  - Receptors, Dopamine D2/*drug effects
MH  - Serotonin Agents/*pharmacology
EDAT- 2011/06/30 06:00
MHDA- 2011/11/16 06:00
CRDT- 2011/06/30 06:00
PHST- 2011/06/30 06:00 [entrez]
PHST- 2011/06/30 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
AID - 10.1097/FBP.0b013e3283487346 [doi]
PST - ppublish
SO  - Behav Pharmacol. 2011 Aug;22(4):362-9. doi: 10.1097/FBP.0b013e3283487346.