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  • Title: Fibroblast growth factor-1 within the ventral tegmental area participates in motor sensitizing effects of morphine.
    Author: Flores JA, Galan-Rodriguez B, Rojo AI, Ramiro-Fuentes S, Cuadrado A, Fernandez-Espejo E.
    Journal: Neuroscience; 2010 Jan 13; 165(1):198-211. PubMed ID: 19819303.
    Abstract:
    Drug addiction is viewed as a form of neural plasticity, and neurotrophic factors have been implicated in many forms of plasticity in the adult nervous system. Here we show that the fibroblast growth factor-1 (FGF-1), that is expressed on dopamine and GABA neurons of the ventral tegmental area (VTA), is involved in the sensitizing effects of morphine. The receptor FGFR-1 is expressed on VTA astrocytes, as well as dopamine and GABA neurons. FGF-1 or anti-FGF-1 infusions into the VTA during the induction (not expression) phase of sensitization advanced or blocked morphine's activating motor effects respectively, in a dose-dependent manner. Infusions into the adjacent substantia nigra, whose neurons also express FGF-1 and FGFR-1, did not modify normal morphine-induced sensitization. Biochemical traits related to morphine's sensitizing effects were altered by intra-VTA anti-FGF-1 because morphine-induced upregulation of both tyrosine hydroxylase (TH) and N-methyl d-aspartate glutamate receptor 1 (NMDAR1) in the VTA was blocked after anti-FGF-1. Changes in the activation state of VTA calcium/calmodulin-dependent kinase type II seem to participate in FGF-1-induced effects as well. We conclude that the FGF-1 system of the ventral tegmental area is required for biochemical and behavioral sensitization to this drug.
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