title: Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal.
abstract: Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr1 and Pitx3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real-time polymerase chain reaction, immunofluorescence and Western blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters (DAT), vesicular monoamine transporters (VMAT2) and DA 2 receptor subtype (DRD2), DA 1 receptor subtype as well as tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and/or nucleus accumbens (NAc). In addition, Nurr1 and Pitx3 expression was also measured. Present data showed a high degree of colocalization of Nurr1 and Pitx3 with TH(+) neurons in the VTA. We found that the increased Nurr1 and/or Pitx3 levels during morphine dependence and in morphine-withdrawn rats were associated to an increase of DAT, VMAT2 and DRD2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug-reward pathways, suggesting that Nurr1 and Pitx3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal-induced alterations of DA neurons activity in the mesolimbic pathway.
authors.affiliation: Group of Cellular and Molecular Pharmacology, Campus de Espinardo, University of Murcia, Spain.|IMIB, Instituto Murciano de Investigación Biosanitaria, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Pérez
authors.affiliation: Group of Cellular and Molecular Pharmacology, Campus de Espinardo, University of Murcia, Spain.|IMIB, Instituto Murciano de Investigación Biosanitaria, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Núñez
authors.affiliation: Group of Cellular and Molecular Pharmacology, Campus de Espinardo, University of Murcia, Spain.|IMIB, Instituto Murciano de Investigación Biosanitaria, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Laorden
authors.affiliation: Group of Cellular and Molecular Pharmacology, Campus de Espinardo, University of Murcia, Spain.|IMIB, Instituto Murciano de Investigación Biosanitaria, Spain.
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Milanés
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004343:Drug Implants; D018398:Homeodomain Proteins; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000209:etiology* / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000378:metabolism; D014157:Transcription Factors; D017557:Ventral Tegmental Area / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; C000607792:DRD2 protein, rat; D050483:Dopamine Plasma Membrane Transport Proteins; D004343:Drug Implants; D018398:Homeodomain Proteins; D009292:Narcotic Antagonists; D009294:Narcotics; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; C493454:Slc18a2 protein, rat; D014157:Transcription Factors; D050493:Vesicular Monoamine Transport Proteins; C433629:homeobox protein PITX3; D009270:Naloxone; D009020:Morphine; D004298:Dopamine
keywords: Dopamine markers; opiates dependence and withdrawal; reward pathway