BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization.
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 body. A more diverse role for BDNF has emerged progressively from observations showing that it is also transported anterogradely, is released on neuron depolarization, and triggers rapid intracellular signals and action potentials in central neurons. 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 accumbens both during development and in adulthood. BDNF from corticostriatal neurons also induces behavioural sensitization, by triggering overexpression of the D3 receptor in striatum of hemiparkinsonian rats. Our results suggest that BDNF may be an important determinant of pathophysiological conditions such as drug addiction, schizophrenia or Parkinson's disease, in which D3 receptor expression is abnormal.
Guillin
O
O
Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 109, Centre Paul Broca, 2ter rue d'Alésia, 75014 Paris, France.
Diaz
J
J
Carroll
P
P
Griffon
N
N
Schwartz
J C
JC
Sokoloff
P
P
D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D005625:Frontal Lobe / Q000502:physiology; D018390:Gene Targeting; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D050637:Receptors, Dopamine D3; D017557:Ventral Tegmental Area / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; C493594:Drd3 protein, mouse; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D007980:Levodopa; D016627:Oxidopamine; D020813:Receptor, trkB; D004298:Dopamine