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(1) receptors (CB(1)Rs) in the striatum, a brain area in which both BDNF and CB(1)s play a role in the emotional consequences of stress and of rewarding experiences. BDNF potently inhibited CB(1)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(1)Rs controlling GABA-mediated IPSCs (CB(1)R(GABA)), whereas CB(1)Rs modulating glutamate transmission and GABA(B) receptors were not affected. The action of BDNF on CB(1)R(GABA) 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(+/-)), CB(1)R(GABA) responses were potentiated and were preserved from the action of haloperidol, a DA D(2) receptor (D(2)R) antagonist able to fully abolish CB(1)R(GABA) function in rewarded animals. Haloperidol also enhanced BDNF levels in the striatum, suggesting that this neurotrophin may act as a downstream effector of D(2)Rs in the modulation of cannabinoid signaling. Accordingly, 5 d cocaine exposure both reduced striatal BDNF levels and increased CB(1)R(GABA) activity, through a mechanism dependent on D(2)Rs. The present study identifies a novel mechanism of CB(1)R regulation mediated by BDNF and cholesterol metabolism and provides some evidence that DA D(2)R-dependent modulation of striatal CB(1)R activity is mediated by this neurotrophin.
De Chiara, V., Angelucci, F., Rossi, S., Musella, A., Cavasinni, F., Cantarella, C., et al. (2010). Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum. THE JOURNAL OF NEUROSCIENCE, 30(24), 8127-8137 [10.1523/JNEUROSCI.1683-10.2010].
|Tipologia:||Articolo su rivista|
|Citazione:||De Chiara, V., Angelucci, F., Rossi, S., Musella, A., Cavasinni, F., Cantarella, C., et al. (2010). Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum. THE JOURNAL OF NEUROSCIENCE, 30(24), 8127-8137 [10.1523/JNEUROSCI.1683-10.2010].|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1523/JNEUROSCI.1683-10.2010|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||16-giu-2010|
|Titolo:||Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum|
|Autori:||De Chiara, V; Angelucci, F; Rossi, S; Musella, A; Cavasinni, F; Cantarella, C; Mataluni, G; Sacchetti, L; Napolitano, F; Castelli, M; Caltagirone, C; Bernardi, G; Maccarrone, M; Usiello, A; Centonze, D|
|Appare nelle tipologie:||01 - Articolo su rivista|