PMID- 34233202 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20240116 IS - 1873-7064 (Electronic) IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 196 DP - 2021 Sep 15 TI - Binge ethanol drinking associated with sex-dependent plasticity of neurons in the insula that project to the bed nucleus of the stria terminalis. PG - 108695 LID - S0028-3908(21)00250-1 [pii] LID - 10.1016/j.neuropharm.2021.108695 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Marino, Rosa A M AU - Marino RAM AD - Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. FAU - Girven, Kasey S AU - Girven KS AD - Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, 21201, USA. FAU - Figueiredo, Antonio AU - Figueiredo A AD - Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, 21201, USA. FAU - Navarrete, Jovana AU - Navarrete J AD - Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. FAU - Doty, Carolyn AU - Doty C AD - Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, 21201, USA. FAU - Sparta, Dennis R AU - Sparta DR AD - Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, 21201, USA. Electronic address: dsparta@som.umaryland.edu. LA - eng GR - F31 DA047050/DA/NIDA NIH HHS/United States GR - R00 AA021417/AA/NIAAA NIH HHS/United States GR - R01 AA027516/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210704 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Central Nervous System Depressants) RN - 3K9958V90M (Ethanol) SB - IM MH - Alcohol Abstinence MH - Animals MH - Binge Drinking/*metabolism/physiopathology MH - Central Nervous System Depressants/administration & dosage/pharmacology MH - Ethanol/administration & dosage/pharmacology MH - Female MH - Insular Cortex/*metabolism/physiopathology MH - Male MH - Mice MH - Neural Pathways MH - Neuronal Plasticity/*physiology MH - Neurons/*metabolism/physiology MH - Patch-Clamp Techniques MH - Septal Nuclei/*metabolism/physiopathology MH - Sex Characteristics MH - Sex Factors PMC - PMC8928450 MID - NIHMS1723355 OTO - NOTNLM OT - BNST OT - Binge ethanol drinking OT - Electrophysiology OT - Insula OT - Sex difference EDAT- 2021/07/08 06:00 MHDA- 2022/02/03 06:00 PMCR- 2022/09/15 CRDT- 2021/07/07 20:08 PHST- 2020/12/22 00:00 [received] PHST- 2021/05/26 00:00 [revised] PHST- 2021/06/30 00:00 [accepted] PHST- 2021/07/08 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] PHST- 2021/07/07 20:08 [entrez] PHST- 2022/09/15 00:00 [pmc-release] AID - S0028-3908(21)00250-1 [pii] AID - 10.1016/j.neuropharm.2021.108695 [doi] PST - ppublish SO - Neuropharmacology. 2021 Sep 15;196:108695. doi: 10.1016/j.neuropharm.2021.108695. Epub 2021 Jul 4.