期刊
NEUROPHARMACOLOGY
卷 196, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2021.108695
关键词
Binge ethanol drinking; Insula; BNST; Electrophysiology; Sex difference
资金
- NIH/NIAAA [R01 AA 027516 R00 AA021417]
- NIH/NIDA [F31 DA 047050]
Changes in brain regions involved in reward-seeking may contribute to persistent behaviors associated with alcohol-use disorder. The BNST is a critical node linked to alcohol consumption and anxiety-related disorders. Previous research suggests that the IC-vBNST projection is important in emotional and reward-seeking processes.
Modifications in brain regions that govern reward-seeking are thought to contribute to persistent behaviors that are heavily associated with alcohol-use disorder (AUD) including binge ethanol drinking. The bed nucleus of the stria terminalis (BNST) is a critical node linked to both alcohol consumption and the onset, maintenance and progression of adaptive anxiety and stress-related disorders. Differences in anatomy, connectivity and receptor subpopulations, make the BNST a sexually dimorphic region. Previous work indicates that the ventral BNST (vBNST) receives input from the insular cortex (IC), a brain region involved in processing the body's internal state. This IC-vBNST projection has also been implicated in emotional and reward-seeking processes. Therefore, we examined the functional properties of vBNST-projecting, IC neurons in male and female mice that have undergone short-term ethanol exposure and abstinence using a voluntary Drinking in the Dark paradigm (DID) paired with whole-cell slice electrophysiology. First we show that IC neurons projected predominantly to the vBNST. Next, our data show that short-term ethanol exposure and abstinence enhanced excitatory synaptic strength onto vBNST-projecting, IC neurons in both sexes. However, we observed diametrically opposing modifications in excitability across sexes. In particular, short-term ethanol exposure resulted in increased intrinsic excitability of vBNST-projecting, IC neurons in females but not in males. Furthermore, in females, abstinence decreased the excitability of these same neurons. Taken together these findings show that short-term ethanol exposure, as well as the abstinence cause sex-related adaptations in BNST-projecting, IC neurons.
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