Browsing by Subject "Pitx3"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Open Access
    Dysregulation of dopaminergic regulatory mechanisms in the mesolimbic pathway induced by morphine and morphine withdrawal
    (Springer, 2015) López Bellido, Roger; Rodríguez, Raquel E.; Núñez Parra, Cristina; García Pérez, Daniel; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología; Facultades de la UMU::Facultad de Medicina
    Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. 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. The aim of our study was to investigate abnormalities in the mesolimbic pathway associated with morphine dependence and withdrawal. Using quantitative real-time PCR, immunofluorescence, HPLC and Western blotting, here we studied the effects of single morphine administration, morphine dependence and morphine withdrawal on Nurr1 and Pitx3 expression as well as on the DA marker tyrosine hydroxylase (TH) and the turnover of DA in the ventral tegmental area (VTA) and/or nucleus accumbens. We showed that the three experimental conditions caused induction of Nurr1 and Pitx3 in the VTA, which correlated with changes in TH expression during chronic morphine administration. Present data also confirmed the colocalization of Nurr1 and Pitx3 with TH-positive neurons in the posterior VTA. Furthermore, during morphine dependence, Nurr1 was detected in the nucleus compartment of VTA TH-positive neurons, whereas Pitx3 was strongly detected in the nucleus of TH-positive neurons after single morphine administration and during morphine withdrawal. The number of TH neurons, number of Nurr1 or Pitx3-positive cells, and the number of TH neurons expressing Nurr1 or Pitx3 were not modified in the subpopulations of DA neurons. Present data provide novel insight into the potential correlation between Nurr1 and Pitx3 and DA neurons plasticity during opiate addiction in the mesolimbic pathway.
  • Thumbnail Image
    Publication
    Restricted
    Morphine administration modulates expression of Argonaute 2 and dopamine-related transcription factors involved in midbrain dopaminergic neurons function
    (Wiley : British Pharmacological Society, 2012-12-05) García Pérez, Daniel; Sáez Belmonte, F.; Núñez Parra, Cristina; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología; Facultades de la UMU::Facultad de Medicina
    Background and Purpose Alterations in transcription factors that regulate the development and maintenance of dopamine (DA) neurons (such as Nurr1 and Pitx3) play an important role in the pathogenesis of addiction diseases. We have examined the effects of acute and chronic morphine and morphine withdrawal on TH expression and activity as well as expression of Nurr1, Pitx3 and Ago2 in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of the rat. Experimental Approach Rats were injected acutely with morphine and decapitated 1 or 2 h later. Another set of rats were made dependent on morphine by implantation of two morphine pellets. Precipitated withdrawal was induced by injection of naloxone. Ago2, Pitx3, Nurr1, total TH (tTH), TH phosphorylated at Ser31 and at Ser40, and 3,4-Dihydroxyphenylacetic acid, and DA determination in the VTA and/or NAc were measured using immunoblotting, HPLC and immunofluorescence. Key Results Acute morphine produced a marked increase in TH activity and DA turnover in the NAc, concomitantly with increased Nurr1 and Pitx3 expression in the VTA. In contrast, precipitated morphine withdrawal decreased TH activation, TH expression and did not increase DA turnover in the NAc. These effects paralleled decreases in Ago2 expression, which was accompanied by increased Nurr1 and Pitx3, TH activity and normalized TH protein levels in the VTA. Conclusions and Implications The combined decrease in Ago2 and increases in Nurr1 and Pitx3 might represent some of the mechanisms that served to protect against accumbal TH regulation observed in morphine withdrawn rats, which may be critical for DA bioavailability to influence behaviour.