Inhibition of FGF Receptor-1 Suppresses Alcohol Consumption: Role of PI3 Kinase Signaling in Dorsomedial Striatum

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Oren Even-Chen, Segev Barak

Abstract

Excessive alcohol intake leads to mesostriatal neuroadaptations, and to addiction phenotypes. We recently found in rodents that alcohol increases fibroblast growth factor 2 (FGF2) expression in the dorsomedial striatum (DMS), which promotes alcohol consumption. Here, we show that systemic or intra-DMS blockade of the FGF2 receptor, FGF receptor-1 (FGFR1), suppresses alcohol consumption, and that the effects of FGF2-FGFR1 on alcohol drinking are mediated via the phosphoinositide 3 kinase (PI3K) signaling pathway. Specifically, we found that sub-chronic alcohol treatment (7 d × 2.5 g/kg, i.p.) increased Fgfr1 mRNA expression in the dorsal hippocampus and dorsal striatum. However, prolonged and excessive voluntary alcohol consumption in a two-bottle choice procedure increased Fgfr1 expression selectively in DMS. Importantly, systemic administration of the FGFR1 inhibitor PD173074 to mice, as well as its infusion into the DMS of rats, decreased alcohol consumption and preference, with no effects on natural reward consumption. Finally, inhibition of the PI3K, but not of the mitogen-activated protein kinase (MAPK) signaling pathway, blocked the effects of FGF2 on alcohol intake and preference. Our results suggest that activation of F...Continue Reading

Citations

Oct 17, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Kana Hamada, Amy W Lasek
Jan 23, 2020·Cold Spring Harbor Perspectives in Medicine·Mirit LiranSegev Barak
Aug 26, 2021·Neuroscience Letters·Eliyahu DremencovSaak V Ovsepian
Nov 20, 2021·Addiction Biology·Oren Even-ChenSegev Barak

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