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  • Title: Assessment of ventral tegmental area-projecting GABAergic neurons from the bed nucleus of the stria terminalis in modulating binge-like ethanol intake.
    Author: Companion MA, Thiele TE.
    Journal: Eur J Neurosci; 2018 Dec; 48(11):3335-3343. PubMed ID: 30362199.
    Abstract:
    Corticotropin-releasing factor (CRF) circuitry is a key component in plasticity underlying the transition to ethanol (EtOH) dependence. We have previously shown that chemogenetic silencing of CRF neurons stemming from the dorsolateral bed nucleus of the stria terminalis (dlBNST) and projecting to the ventral tegmental area (VTA) significantly blunts binge-like EtOH consumption. While CRF neurons in the BNST are thought to entail primarily a GABA phenotype, glutamatergic neurons within the BNST also innervate the VTA and influence consummatory behaviors. Here, we combined the well-validated Vgat-ires-Cre transgenic mice with chemogenetic tools to extend our previous findings and corroborate the contribution of the VTA-projecting dlBNST GABAergic circuitry in modulating binge-like EtOH consumption using "drinking-in-the-dark" procedures. Mice were given bilateral injection of Gi-coupled chemogenetic viral vector (or control virus) into the dlBNST and bilateral cannulae into the VTA. On test day, clozapine-N-oxide (CNO; or vehicle) was infused directly into the VTA to silence VTA-projecting dlBNST neurons and subsequent binge-like EtOH consumption was assessed. We then used immunohistochemistry (IHC) to determine the co-expression of CRF and viral vector. Our results showed that relative to vehicle treatment or CNO treatment in mice expressing the control virus, silencing VTA-projecting dlBNST GABAergic neurons by CNO treatment in mice expressing Gi-coupled chemogenetic virus significantly reduced binge-like EtOH intake. This effect was not seen with sucrose consumption. Our IHC results confirm a population of CRF-expressing GABAergic neurons within the dlBNST. This study directly establishes that VTA-projecting GABAergic neurons of the dlBNST modulate binge-like EtOH consumption.
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