title: BDNF-mediated regulation of ethanol consumption requires the activation of the MAP kinase pathway and protein synthesis.
abstract: We previously found that the brain-derived neurotrophic factor (BDNF) in the dorsolateral striatum (DLS) is part of a homeostatic pathway that gates ethanol self-administration [Jeanblanc et al. (2009). J Neurosci, 29, 13494-13502)]. Specifically, we showed that moderate levels (10%) of ethanol consumption increase BDNF expression within the DLS, and that direct infusion of BDNF into the DLS decreases operant self-administration of a 10% ethanol solution. BDNF binding to its receptor, TrkB, activates the mitogen-activated protein kinase (MAPK), phospholipase C-γ (PLC-γ) and phosphatidylinositol 3-kinase (PI3K) pathways. Thus, here, we set out to identify which of these intracellular pathway(s) plays a role in the regulation of ethanol consumption by BDNF. We found that inhibition of the MAPK, but not PLC-γ or PI3K, activity blocks the BDNF-mediated reduction of ethanol consumption. As activation of the MAPK pathway leads to the initiation of transcription and/or translation events, we tested whether the BDNF-mediated reduction of ethanol self-administration requires de novo protein synthesis. We found that the inhibitory effect of BDNF on ethanol intake is blocked by the protein synthesis inhibitor cycloheximide. Together, our results show that BDNF attenuates ethanol drinking via activation of the MAPK pathway in a protein synthesis-dependent manner within the DLS.
authors.affiliation: Gallo Research Center, University of California, San Francisco, Emeryville, CA, 94608, USA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Jeanblanc
authors.forename: Marian L
authors.initials: ML
authors.lastname: Logrip
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
authors.forename: Dorit
authors.initials: D
authors.lastname: Ron
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant; D000431:Ethanol / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D000431:Ethanol