Brain-derived neurotrophic factor controls dopamine D3 receptor expression: implications for neurodevelopmental psychiatric disorders.

Brain-derived neurotrophic factor (BDNF) belongs to a family of proteins related to nerve growth factor, which are responsible for neuron proliferation, survival and differentiation. A more diverse role for BDNF as a neuronal extracellular transmitter has, nevertheless, been proposed. The dopamine D(3) receptor has been implicated in neuropsychiatric disorders including schizophrenia, drug addiction, depression and Parkinson's disease. Its expression during development and in adulthood is highly dependent on dopaminergic innervation. Here we show that BDNF synthesized by dopamine neurons is responsible for the appearance of the D(3) receptor during development and maintains D(3) receptor expression in adults. Moreover, BDNF triggers D(3) receptor overexpression and behavioral sensitization to levodopa in denervated animals. These results suggest that BDNF, by controlling the expression of specific genes such as the D(3) receptor gene, may be an important factor in neurodevelopmental psychiatric diseases.