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Assessment of ventral tegmental area‐projecting GABA ergic neurons from the bed nucleus of the stria terminalis in modulating binge‐like ethanol intake
Author(s) -
Companion Michel A.,
Thiele Todd E.
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14222
Subject(s) - ventral tegmental area , stria terminalis , extended amygdala , gabaergic , neuroscience , glutamatergic , medicine , endocrinology , biology , nucleus , inhibitory postsynaptic potential , dopamine , glutamate receptor , dopaminergic , receptor
Corticotropin‐releasing factor ( CRF ) circuitry is a key component in plasticity underlying the transition to ethanol (Et OH ) dependence. We have previously shown that chemogenetic silencing of CRF neurons stemming from the dorsolateral bed nucleus of the stria terminalis (dl BNST ) and projecting to the ventral tegmental area ( VTA ) significantly blunts binge‐like Et OH 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 dl BNST GABA ergic circuitry in modulating binge‐like Et OH consumption using “drinking‐in‐the‐dark” procedures. Mice were given bilateral injection of Gi‐coupled chemogenetic viral vector (or control virus) into the dl BNST 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 dl BNST neurons and subsequent binge‐like Et OH 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 dl BNST GABA ergic neurons by CNO treatment in mice expressing Gi‐coupled chemogenetic virus significantly reduced binge‐like Et OH intake. This effect was not seen with sucrose consumption. Our IHC results confirm a population of CRF ‐expressing GABA ergic neurons within the dl BNST . This study directly establishes that VTA ‐projecting GABA ergic neurons of the dl BNST modulate binge‐like Et OH consumption.

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