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Título: | Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice |
Autor: | Gómez-Sintes, Raquel CSIC ORCID ; Bortolozzi, Analía CSIC ORCID; Artigas, Francesc CSIC ORCID; Lucas, José Javier CSIC ORCID | Palabras clave: | Basal ganglia Schizophrenia Dorsal striatum Glycogen synthase kinase-3 (GSK-3) Dopamine receptors |
Fecha de publicación: | sep-2014 | Editor: | Elsevier | Citación: | European Neuropsychopharmacology 24(9): 1524-1533 (2014) | Resumen: | Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer's disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. © 2014 Elsevier B.V. and ECNP. | Versión del editor: | http://dx.doi.org/10.1016/j.euroneuro.2014.07.004 | URI: | http://hdl.handle.net/10261/112775 | DOI: | 10.1016/j.euroneuro.2014.07.004 | Identificadores: | doi: 10.1016/j.euroneuro.2014.07.004 issn: 1873-7862 |
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