Fibroblast growth factor-1 within the ventral tegmental area participates in motor sensitizing effects of morphine

Neuroscience. 2010 Jan 13;165(1):198-211. doi: 10.1016/j.neuroscience.2009.10.009. Epub 2009 Oct 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Astrocytes / metabolism
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / biosynthesis
  • Dopamine / metabolism
  • Fibroblast Growth Factor 1 / immunology
  • Fibroblast Growth Factor 1 / pharmacology
  • Fibroblast Growth Factor 1 / physiology*
  • JNK Mitogen-Activated Protein Kinases / biosynthesis
  • Male
  • Mitogen-Activated Protein Kinase 1 / biosynthesis
  • Mitogen-Activated Protein Kinase 3 / biosynthesis
  • Morphine / pharmacology*
  • Motor Activity / drug effects*
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Tyrosine 3-Monooxygenase / biosynthesis
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / physiology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Antibodies
  • NMDA receptor A1
  • Receptors, N-Methyl-D-Aspartate
  • Fibroblast Growth Factor 1
  • gamma-Aminobutyric Acid
  • Morphine
  • Tyrosine 3-Monooxygenase
  • Receptor, Fibroblast Growth Factor, Type 1
  • Proto-Oncogene Proteins c-akt
  • Cyclic AMP-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Dopamine