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Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum.
- Source :
- Journal of Neuroscience; 6/16/2010, Vol. 30 Issue 24, p8127-8137, 11p, 7 Graphs
- Publication Year :
- 2010
-
Abstract
- The role of brain-derived neurotrophic factor (BDNF) in emotional processes suggests an interaction with the endocannabinoid system. Here, we addressed the functional interplay between BDNF and cannabinoid CB<subscript>1</subscript> receptors (CB<subscript>1</subscript>Rs) in the striatum, a brain area in which both BDNF and CB<subscript>1</subscript>s play a role in the emotional consequences of stress and of rewarding experiences. BDNF potently inhibited CB<subscript>1</subscript>R function in the striatum, through a mechanism mediated by altered cholesterol metabolism and membrane lipid raft function. The effect of BDNF was restricted to CB<subscript>1</subscript>Rs controlling GABA-mediated IPSCs (CB<subscript>1</subscript>R<subscript>(GABA)</subscript>), whereas CB<subscript>1</subscript>Rs modulating glutamate transmission and GABA<subscript>B</subscript> receptors were not affected. The action of BDNF on CB<subscript>1</subscript>R<subscript>(GABA)</subscript> function was tyrosine kinase dependent and was complete even after receptor sensitization with cocaine or environmental manipulations activating the dopamine (DA)-dependent reward system. In mice lacking one copy of the BDNF gene (BDNF<superscript>+/-</superscript>), CB<subscript>1</subscript>R<subscript>(GABA)</subscript> responses were potentiated and were preserved from the action of haloperidol, a DA D<subscript>2</subscript> receptor (D<subscript>2</subscript>R) antagonist able to fully abolish CB<subscript>1</subscript>R(<subscript>GABA)</subscript> function in rewarded animals. Haloperidol also enhanced BDNF levels in the striatum, suggesting that this neurotrophin may act as a downstream effector of D<subscript>2</subscript>Rs in the modulation of cannabinoid signaling. Accordingly, 5 d cocaine exposure both reduced striatal BDNF levels and increased CB<subscript>1</subscript>R<subscript>(GABA)</subscript> activity, through a mechanism dependent on D<subscript>2</subscript>Rs. The present study identifies a novel mechanism of CB<subscript>1</subscript>R regulation mediated by BDNF and cholesterol metabolism and provides some evidence that DA D<subscript>2</subscript>R-dependent modulation of striatal CB<subscript>1</subscript>R activity is mediated by this neurotrophin. [ABSTRACT FROM AUTHOR]
- Subjects :
- BRAIN
NEUROTROPHINS
EMOTIONS
GABA
CHOLESTEROL metabolism
DOPAMINE
LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 30
- Issue :
- 24
- Database :
- Complementary Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 52221250
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.1683-10.2010