Brain-Derived Neurotrophic Factor in an Orbitofrontal Cortical-Dorsolateral Striatal Circuit Gates Alcohol Consumption

Abstract

Brain-derived neurotrophic factor (BDNF) signaling in the dorsolateral striatum (DLS) gates alcohol self-administration in rodents. The major source of BDNF in the striatum is the cortex, and we recently found that BDNF-expressing neurons in the ventrolateral orbitofrontal cortex (vlOFC) extend axonal projections to the DLS. We therefore hypothesized that BDNF in the vlOFC to DLS circuit moderates alcohol intake. We show that overexpression of BDNF in the vlOFC, which activates BDNF signaling in the DLS, is sufficient to attenuate voluntary consumption and seeking of 20% alcohol in the home cage using a two-bottle choice paradigm. Overexpressing BDNF in the vlOFC had no effect on the consumption of a sweetened saccharin solution. In addition, BDNF overexpression in the neighboring motor cortex did not alter alcohol intake. Finally, pathway-specific overexpression of BDNF in DLS-projecting vlOFC neurons significantly reduced alcohol intake and preference. Overall, BDNF in the vlOFC, and specifically in a vlOFC-DLS pathway, keeps alcohol drinking in moderation.

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

“…In addition, sex differences in social behavior have been widely described [50][51][52][53][54][55]. However, further studies are needed to determine whether BDNF in female mice plays a role in other behaviors, including gating alcohol use, which is mediated in part via corticostriatal circuitries in male mice [14,[56][57][58].…”

“…These data suggest that sex differences may be more generalized in mice carrying the Met68BDNF allele. However, further studies are needed to determine whether BDNF in female mice plays a role in other behaviors, including gating alcohol use, which is mediated in part via corticostriatal circuitries in male mice [14,[61][62][63].…”