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BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization

Olivier Guillin, Jorge Diaz, Patrick Carroll, Nathalie Griffon, Jean-Charles Schwartz and Pierre Sokoloff
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Olivier Guillin: Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 109, Centre Paul Broca
Jorge Diaz: Laboratoire de Physiologie, Université René Descartes
Patrick Carroll: Unité de Développement et Pathologie du Motoneurone Spinal, INSERM U 382, IBDM, Campus de Luminy
Nathalie Griffon: Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 109, Centre Paul Broca
Jean-Charles Schwartz: Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 109, Centre Paul Broca
Pierre Sokoloff: Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 109, Centre Paul Broca

Nature, 2001, vol. 411, issue 6833, 86-89

Abstract: Abstract Brain-derived neurotrophic factor (BDNF), like other neurotrophins, is a polypeptidic factor initially regarded to be responsible for neuron proliferation, differentiation and survival, through its uptake at nerve terminals and retrograde transport to the cell body1. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely2,3, is released on neuron depolarization1, and triggers rapid intracellular signals4 and action potentials in central neurons5. Here we report that BDNF elicits long-term neuronal adaptations by controlling the responsiveness of its target neurons to the important neurotransmitter, dopamine. Using lesions and gene-targeted mice lacking BDNF, we show that BDNF from dopamine neurons is responsible for inducing normal expression of the dopamine D3 receptor in nucleus accumbens6,7,8 both during development and in adulthood. BDNF from corticostriatal neurons3 also induces behavioural sensitization, by triggering overexpression of the D3 receptor in striatum of hemiparkinsonian rats9. Our results suggest that BDNF may be an important determinant of pathophysiological conditions such as drug addiction10, schizophrenia11 or Parkinson's disease12, in which D3 receptor expression is abnormal.

Date: 2001
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DOI: 10.1038/35075076

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