Sex differences in neuronal activation in the cortex and midbrain during quinine-adulterated alcohol intake.

IF 2.1 4区 医学 Q3 SUBSTANCE ABUSE
Miranda E Arnold, Jesse R Schank
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引用次数: 0

Abstract

Aims: Continued alcohol consumption despite negative consequences is a core symptom of alcohol use disorder. This is modeled in mice by pairing negative stimuli with alcohol, such as adulterating alcohol solution with quinine. Mice consuming alcohol under these conditions are considered to be engaging in aversion-resistant intake. Previously, we have observed sex differences in this behavior, with females more readily expressing aversion-resistant consumption. We also identified three brain regions that exhibited sex differences in neuronal activation during quinine-alcohol drinking: ventromedial prefrontal cortex (vmPFC), posterior insular cortex (PIC), and ventral tegmental area (VTA). Specifically, male mice showed increased activation in vmPFC and PIC, while females exhibited increased activation in VTA. In this study, we aimed to identify what specific type of neurons are activated in these regions during quinine-alcohol drinking.

Method: We assessed quinine-adulterated alcohol intake using the two-bottle choice procedure. We also utilized RNAscope in situ hybridization in the three brain regions that previously exhibited a sex difference to examine colocalization of Fos, glutamate, GABA, and dopamine.

Result: Females showed increased aversion-resistant alcohol consumption compared to males. We also found that males had higher colocalization of glutamate and Fos in vmPFC and PIC, while females had greater dopamine and Fos colocalization in the VTA.

Conclusions: Collectively, these experiments suggest that glutamatergic output from the vmPFC and PIC may have a role in suppressing, and dopaminergic activity in the VTA may promote, aversion-resistant alcohol consumption. Future experiments will examine neuronal circuits that contribute to sex differences in aversion resistant consumption.

摄入奎宁掺杂酒精时大脑皮层和中脑神经元激活的性别差异
目的:不顾不良后果继续饮酒是酒精使用障碍的核心症状。通过将负面刺激与酒精配对,例如在酒精溶液中掺入奎宁,可以在小鼠身上模拟出这种情况。在这些条件下饮酒的小鼠被认为是在进行厌恶抵抗摄入。在此之前,我们已经观察到了这种行为的性别差异,雌性小鼠更容易表现出厌恶-抵抗性摄入。我们还发现了在饮用奎宁酒精时神经元激活存在性别差异的三个脑区:腹外侧前额叶皮层(vmPFC)、后岛叶皮层(PIC)和腹侧被盖区(VTA)。具体来说,雄性小鼠的腹外侧前额叶皮层和岛叶后部皮层的激活增加,而雌性小鼠的腹侧延髓区的激活增加。在这项研究中,我们的目的是确定在饮奎宁酒精时,这些区域中激活的神经元的具体类型:方法:我们采用双瓶选择法评估了奎宁掺杂酒精的摄入量。我们还利用 RNAscope 原位杂交技术,在之前表现出性别差异的三个脑区检测了 Fos、谷氨酸、GABA 和多巴胺的共定位:结果:与男性相比,女性对酒精的厌恶抵抗力更强。我们还发现,男性的谷氨酸和Fos在vmPFC和PIC有更高的共定位,而女性的多巴胺和Fos在VTA有更高的共定位:总之,这些实验表明,vmPFC 和 PIC 的谷氨酸能输出可能在抑制厌恶型酒精消费中发挥作用,而 VTA 中的多巴胺能活动可能促进厌恶型酒精消费。未来的实验将研究导致抗厌恶性消费性别差异的神经元回路。
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来源期刊
Alcohol and alcoholism
Alcohol and alcoholism 医学-药物滥用
CiteScore
4.70
自引率
3.60%
发文量
62
审稿时长
4-8 weeks
期刊介绍: About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.
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