PMID- 21181116
OWN - NLM
STAT- MEDLINE
DCOM- 20110506
LR  - 20231213
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 383
IP  - 2
DP  - 2011 Feb
TI  - Regulation of opioid gene expression in the rat brainstem by 
      3,4-methylenedioxymethamphetamine (MDMA): role of serotonin and involvement of 
      CREB and ERK cascade.
PG  - 169-78
LID - 10.1007/s00210-010-0587-5 [doi]
AB  - The amphetamine analogue 3,4-methylendioxymetamphetamine (MDMA, Ecstasy) causes 
      complex adaptations at the molecular and cellular levels altering the activity of 
      different brain neurotransmitters. The present study aims to verify the effects 
      of single and repeated injections of MDMA on dynorphin and nociceptin systems 
      gene regulation in the brainstem, an area rich in neurons containing serotonin. 
      Both acute and chronic (twice a day for 7 days) MDMA (8 mg/kg) induced a marked 
      increase in prodynorphin mRNA levels as well as in cAMP response element-binding 
      protein (CREB) and extracellular signal-regulated kinase-1/2 (ERK1/2) 
      phosphorylation, without causing any effect on kappa opioid receptor or 
      nociceptin system (both pronociceptin and its receptor) genes expression, in this 
      brain region. The blockade of 5HT1/5HT2 receptors by methysergide abolished the 
      acute MDMA-induced increase in prodynorphin. Moreover, the concomitant chronic 
      administration of both methysergide and MDMA (7 days) induced a significant 
      increase in all the dynorphin or nociceptin system genes expression and in CREB 
      and ERK phosphorylation. Our data suggest the involvement of dynorphin in the 
      effects evoked by MDMA in the brainstem, possibly via CREB and ERK1/2 cascade 
      activation, since the ERK inhibitor PD98059 prevented the MDMA-induced 
      prodynorphin gene expression, and, acutely, also through the involvement of 
      serotoninergic mechanisms. Chronically, it is also possible to hypothesize a 
      general inhibitor role of serotonin in the effects evoked by MDMA. Moreover, 
      these findings strengthen the hypothesis, already proposed, of a neuroprotective 
      role for both CREB and dynorphin.
FAU - Di Benedetto, Manuela
AU  - Di Benedetto M
AD  - Department of Pharmacology, Alma Mater Studiorum-University of Bologna, via 
      Irnerio 48, 40126, Bologna, Italy. manuela.dibenedetto@unibo.it
FAU - Bastias Candia, Sussy del Carmen
AU  - Bastias Candia Sdel C
FAU - D'Addario, Claudio
AU  - D'Addario C
FAU - Porticella, Elena Elettra
AU  - Porticella EE
FAU - Cavina, Chiara
AU  - Cavina C
FAU - Candeletti, Sanzio
AU  - Candeletti S
FAU - Romualdi, Patrizia
AU  - Romualdi P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101223
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Enkephalins)
RN  - 0 (Opioid Peptides)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 0 (Receptors, Serotonin, 5-HT1)
RN  - 0 (Receptors, Serotonin, 5-HT2)
RN  - 0 (Serotonin Antagonists)
RN  - 333DO1RDJY (Serotonin)
RN  - 93443-35-7 (preproenkephalin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain Stem/*drug effects/enzymology/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Enkephalins/genetics
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Opioid Peptides/*genetics
MH  - Phosphorylation
MH  - Protein Precursors/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Opioid, kappa/genetics
MH  - Receptors, Serotonin, 5-HT1/metabolism
MH  - Receptors, Serotonin, 5-HT2/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Serotonin/*metabolism
MH  - Serotonin Antagonists/pharmacology
MH  - Signal Transduction
MH  - Nociceptin
EDAT- 2010/12/25 06:00
MHDA- 2011/05/07 06:00
CRDT- 2010/12/25 06:00
PHST- 2010/06/08 00:00 [received]
PHST- 2010/12/01 00:00 [accepted]
PHST- 2010/12/25 06:00 [entrez]
PHST- 2010/12/25 06:00 [pubmed]
PHST- 2011/05/07 06:00 [medline]
AID - 10.1007/s00210-010-0587-5 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2011 Feb;383(2):169-78. doi: 
      10.1007/s00210-010-0587-5. Epub 2010 Dec 23.