Nucleus Millennium in Stress and Addiction

Santiago, Chile

Nucleus Millennium in Stress and Addiction

Santiago, Chile
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Hadweh N.,University of Santiago de Chile | Santibanez M.,Nucleus Millennium in Stress and Addiction | Gonzalez M.P.,Nucleus Millennium in Stress and Addiction | Forray M.I.,Nucleus Millennium in Stress and Addiction | Forray M.I.,University of Santiago de Chile
Behavioural Brain Research | Year: 2010

The present report provides evidence that repeated immobilization stress (RIS) induced a noradrenergic-dependent depressive-like behaviour and an augmented behavioural response to desipramine (DMI), a noradrenaline reuptake inhibitor (NRI), in the forced swimming test (FST). The present results show that RIS decreased the baseline of climbing behaviour in the FST. Whereas subchronic administration of DMI (10. mg/kg, three times in a 24. h period) induced a significantly higher increase in climbing behaviour on repeatedly stressed rats compared to controls. The results also show that the concomitant administration of the low dose of DMI (3. mg/Kg) during the RIS fully prevented the decrease of climbing behaviour induced by RIS, without exerting behavioural effects in control rats, further supporting an augmented response to the DMI antidepressant effects in the repeatedly stressed rats. In conclusion, our data indicate that RIS not only changes the behavioural responses in the FST but also increases the antidepressant effects of DMI. © 2010 Elsevier B.V.


Galleguillos D.,Nucleus Millennium in Stress and Addiction | Galleguillos D.,University of Santiago de Chile | Fuentealba J.A.,Nucleus Millennium in Stress and Addiction | Fuentealba J.A.,University of Santiago de Chile | And 12 more authors.
Journal of Neurochemistry | Year: 2010

Genesis of midbrain dopamine (DA) neurons depends on Nurr1, a nuclear receptor expressed during development and adulthood in these neurons. Nurr1 is required for the expression of genes of dopaminergic phenotype such as tyrosine hydroxylase and DA transporter. The expression of the tyrosine kinase receptor RET also depends on Nurr1 during development. However, it is unknown whether RET expression is regulated by Nurr1 during adulthood, and the mechanism by which Nurr1 regulates RET expression. Using an adeno-associated vector-delivered anti-Nurr1 ribozyme, we knocked-down Nurr1 expression unilaterally in the substantia nigra (SN) of adult rats. Animals injected with the ribozyme displayed a 57.3% decrease in Nurr1 mRNA in the SN accompanied by decreased DA extracellular levels in the striatum. RET mRNA in the injected SN and RET protein in the ipsilateral striatum decreased 76.9% and 47%, respectively. Tyrosine hydroxylase and DA transporter mRNA did not change in Nurr1 knocked-down SN. Nurr1 induced the transcription of the human RET promoter in cell type and concentration-dependent manner. Nurr1 induction of RET promoter is independent of NBRE elements. These results show that the expression of RET in rat adult SN is regulated by Nurr1 and suggest that RET is a transcriptional target of this nuclear receptor. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.


PubMed | Nucleus Millennium in Stress and Addiction
Type: Journal Article | Journal: Journal of neurochemistry | Year: 2010

Genesis of midbrain dopamine (DA) neurons depends on Nurr1, a nuclear receptor expressed during development and adulthood in these neurons. Nurr1 is required for the expression of genes of dopaminergic phenotype such as tyrosine hydroxylase and DA transporter. The expression of the tyrosine kinase receptor RET also depends on Nurr1 during development. However, it is unknown whether RET expression is regulated by Nurr1 during adulthood, and the mechanism by which Nurr1 regulates RET expression. Using an adeno-associated vector-delivered anti-Nurr1 ribozyme, we knocked-down Nurr1 expression unilaterally in the substantia nigra (SN) of adult rats. Animals injected with the ribozyme displayed a 57.3% decrease in Nurr1 mRNA in the SN accompanied by decreased DA extracellular levels in the striatum. RET mRNA in the injected SN and RET protein in the ipsilateral striatum decreased 76.9% and 47%, respectively. Tyrosine hydroxylase and DA transporter mRNA did not change in Nurr1 knocked-down SN. Nurr1 induced the transcription of the human RET promoter in cell type and concentration-dependent manner. Nurr1 induction of RET promoter is independent of NBRE elements. These results show that the expression of RET in rat adult SN is regulated by Nurr1 and suggest that RET is a transcriptional target of this nuclear receptor.

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