BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization

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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.