PMID- 21595923
OWN - NLM
STAT- MEDLINE
DCOM- 20111003
LR  - 20211020
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 8
DP  - 2011 May 19
TI  - Changes in interleukin-1 signal modulators induced by 
      3,4-methylenedioxymethamphetamine (MDMA): regulation by CB2 receptors and 
      implications for neurotoxicity.
PG  - 53
LID - 10.1186/1742-2094-8-53 [doi]
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) produces a neuroinflammatory 
      reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1beta) 
      and microglial activation. The CB2 receptor agonist JWH-015 reduces both these 
      changes and partially protects against MDMA-induced neurotoxicity. We have 
      examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra) levels and 
      IL-1 receptor type I (IL-1RI) expression and the effects of JWH-015. The cellular 
      location of IL-1beta and IL-1RI was also examined. MDMA-treated animals were given 
      the soluble form of IL-1RI (sIL-1RI) and neurotoxic effects examined. METHODS: 
      Dark Agouti rats received MDMA (12.5 mg/kg, i.p.) and levels of IL-1ra and 
      expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p.) 
      was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For 
      localization studies, animals were sacrificed 1 h or 3 h following MDMA and 
      stained for IL-1beta or IL-1RI in combination with neuronal and microglial markers. 
      sIL-1RI (3 mug/animal; i.c.v.) was administered 5 min before MDMA and 3 h later. 
      5-HT transporter density was determined 7 days after MDMA injection. RESULTS: 
      MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in 
      hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression 
      was localized on neuronal cell bodies while IL-1beta expression was observed in 
      microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. 
      MDMA also increased IgG immunostaining indicating that blood brain-barrier 
      permeability was compromised. CONCLUSIONS: In summary, MDMA produces changes in 
      IL-1 signal modulators which are modified by CB2 receptor activation. These 
      results indicate that IL-1beta may play a partial role in MDMA-induced 
      neurotoxicity.
FAU - Torres, Elisa
AU  - Torres E
AD  - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, 
      28040 Madrid, Spain.
FAU - Gutierrez-Lopez, Maria D
AU  - Gutierrez-Lopez MD
FAU - Mayado, Andrea
AU  - Mayado A
FAU - Rubio, Ana
AU  - Rubio A
FAU - O'Shea, Esther
AU  - O'Shea E
FAU - Colado, Maria I
AU  - Colado MI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110519
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Hallucinogens)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Body Temperature/drug effects
MH  - Brain/anatomy & histology/drug effects/metabolism
MH  - Hallucinogens/pharmacology
MH  - Interleukin 1 Receptor Antagonist Protein/*metabolism
MH  - Interleukin-1/*metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurons/cytology/*drug effects/*metabolism
MH  - Rats
MH  - Receptor, Cannabinoid, CB2/*metabolism
MH  - Receptors, Interleukin-1/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Signal Transduction/*physiology
PMC - PMC3113340
EDAT- 2011/05/21 06:00
MHDA- 2011/10/04 06:00
PMCR- 2011/05/19
CRDT- 2011/05/21 06:00
PHST- 2010/12/28 00:00 [received]
PHST- 2011/05/19 00:00 [accepted]
PHST- 2011/05/21 06:00 [entrez]
PHST- 2011/05/21 06:00 [pubmed]
PHST- 2011/10/04 06:00 [medline]
PHST- 2011/05/19 00:00 [pmc-release]
AID - 1742-2094-8-53 [pii]
AID - 10.1186/1742-2094-8-53 [doi]
PST - epublish
SO  - J Neuroinflammation. 2011 May 19;8:53. doi: 10.1186/1742-2094-8-53.