Modulation of MDMA-induced behavioral and transcriptional effects by the delta opioid antagonist naltrindole in mice.
The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only a few studies have focused on the possible interactions between the opioid system and the effects of 3,4-methylenedioxymethamphetamine (MDMA). In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference (CPP) were investigated in the presence of naltrindole (NTI), a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on pro-enkephalin (Penk) and pro-opiomelanocortin (Pomc) gene expression were assessed by real-time quantitative polymerase chain reaction (QPCR). The results showed that, after acute MDMA administration (9 mg/kg; i.p.), NTI (5 mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk gene expression was not modulated by acute MDMA, but a decrease of Pomc gene expression was observed, which was not antagonized by NTI. Administration of the antagonist prevented the acquisition of MDMA-induced CPP, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment, only the level of Pomc was modulated. The observed increase was totally blocked by NTI pre-treatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA.
Belkaï
Emilie
E
Laboratoire de Neuropsychopharmacologie des addictions (INSERM U705, CNRS UMR 7157), Université Paris Descartes, Faculté de Pharmacie, 4 avenue de l'Observatoire, Paris, France.
Scherrmann
Jean-Michel
JM
Noble
Florence
F
Marie-Claire
Cynthia
C
D019969:Amphetamine-Related Disorders / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006213:Hallucinogens / Q000633:toxicity*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D012931:Social Environment; D014158:Transcription, Genetic / Q000187:drug effects*
D004745:Enkephalins; D006213:Hallucinogens; D009292:Narcotic Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; C029992:proenkephalin; D009271:Naltrexone; D011333:Pro-Opiomelanocortin; C055382:naltrindole; D018817:N-Methyl-3,4-methylenedioxyamphetamine