Somatostatin Neurons in the Bed Nucleus of the Stria Terminalis Play a Sex-Dependent Role in Binge Drinking

Abstract

Alcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential.

Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

“…DID was conducted as previously published (Dao et al, 2021;Rhodes et al, 2005;Suresh Nair et al, 2022), at timepoints adapted for adolescence (Holstein et al, 2011;Dao et al, 2020). Mice received 20% (v/v) ethanol (EtOH; Koptec, Decon Labs, King of Prussia, PA) in tap water beginning 3 hr into the dark cycle, for 2 hr (i.e., 10:00 am to 12:00 pm) on three consecutive days.…”

“…The PL cortex was delineated and SST+ were automatically quantified under matched criteria for size, circularity, and intensity consistently with our previously published work (Dao et al, 2020;Suresh Nair et al, 2022).…”