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Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake

Marian L. Logrip^*,, Patricia H. Janak^*,, and Dorit Ron^*,,,1

^* The Gallo Research Center,

Neuroscience Graduate Program, and

Department of Neurology, University of California, San Francisco, Emeryville, California, USA

¹Correspondence: Ernest Gallo Research Center, 5858 Horton St. Ste. 200, Emeryville, CA 94608, USA. E-mail: dorit.ron{at}ucsf.edu

We recently identified brain-derived neurotrophic factor (BDNF) in the dorsal striatum to be a major component of a homeostatic pathway controlling ethanol consumption (1 , 2) . We hypothesized that ethanol-mediated activation of the BDNF signaling cascade is required for the ethanol-related function of the neurotrophic factor. Here, we demonstrate that exposure of striatal neurons to ethanol results in the activation of the BDNF receptor TrkB, leading to the activation of the mitogen-activated protein kinase (MAP kinase) signaling pathway and the subsequent increase in the expression of preprodynorphin (Pdyn) via BDNF. Finally, we show that activation of the dynorphin receptor, the kappa opioid receptor (KOR), is required for the BDNF-mediated decrease in ethanol intake, illustrating a function of dynorphin in BDNF’s homeostatic control of ethanol consumption. Taken together, these results demonstrate that BDNF regulates ethanol intake by initiation of MAP kinase signaling and the ensuing production of downstream gene products, including Pdyn.—Logrip, M. L., Janak, P. H., Ron, D. Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake.

Key Words: MAP kinase • alcohol • addiction • TrkB • ERK