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BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization.
1Unité de Neurobiologie et Pharmacologie Moléculaire, INSERM U 109, Centre Paul Broca, 2ter rue d'Alésia, 75014 Paris, France.
Nature
|May 3, 2001
Summary
Brain-derived neurotrophic factor (BDNF) controls dopamine D3 receptor expression, impacting neuronal adaptation. This finding suggests BDNF
Area of Science:
- Neuroscience
- Molecular Biology
- Neuropharmacology
Background:
- Brain-derived neurotrophic factor (BDNF) is a neurotrophin traditionally linked to neuron survival and growth.
- Emerging evidence indicates BDNF has broader roles, including anterograde transport, release upon depolarization, and rapid signaling in central neurons.
- The precise mechanisms by which BDNF influences neuronal responsiveness to neurotransmitters remain under investigation.
Purpose of the Study:
- To investigate the role of BDNF in modulating neuronal responsiveness to dopamine.
- To determine BDNF's specific contribution to dopamine D3 receptor expression and related behaviors.
- To explore the implications of BDNF-mediated D3 receptor regulation in neurological disorders.
Main Methods:
- Utilized gene-targeted mice lacking BDNF.
- Employed lesion techniques in rodent models.
- Assessed dopamine D3 receptor expression in the nucleus accumbens and striatum.
- Investigated behavioral sensitization in hemiparkinsonian rats.
Main Results:
- BDNF from dopamine neurons is crucial for normal dopamine D3 receptor expression during development and adulthood.
- BDNF derived from corticostriatal neurons induces behavioral sensitization via D3 receptor overexpression in hemiparkinsonian rats.
- BDNF directly controls the responsiveness of target neurons to dopamine.
Conclusions:
- BDNF plays a critical role in regulating dopamine D3 receptor expression, influencing neuronal adaptation.
- Aberrant D3 receptor expression, modulated by BDNF, may underlie conditions like drug addiction, schizophrenia, and Parkinson's disease.
- BDNF represents a significant factor in the pathophysiology of neurological and psychiatric disorders characterized by altered dopamine signaling.
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