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青春期隔离应激和自愿乙醇暴露对成年雄性大鼠乙醇和尼古丁共同使用的影响

Effects of isolation stress and voluntary ethanol exposure during adolescence on ethanol and nicotine co-use in adulthood using male rats.

作者信息

Shaykin Jakob D, Olyha Lydia N, Van Doorn Catherine E, Hales Joshua D, Chandler Cassie M, Hopkins Deann M, Nixon Kimberly, Beckmann Joshua S, Pauly James R, Bardo Michael T

机构信息

Department of Psychology, University of Kentucky, Lexington, KY 40536, USA.

Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Drug Alcohol Depend Rep. 2024 Aug 21;12:100277. doi: 10.1016/j.dadr.2024.100277. eCollection 2024 Sep.

Abstract

BACKGROUND

Alcohol use in adolescence may increase susceptibility to substance use disorders (SUDs) in adulthood. This study determined if voluntary ethanol (EtOH) consumption during adolescence, combined with social isolation, alters the trajectory of EtOH and nicotine intake during adulthood, as well as activating brain neuroinflammation.

METHODS

Adolescent male isolate- and group-housed rats were given 0.2 % saccharin/20 % EtOH (Sacc/EtOH) or water using intermittent 2-bottle choice; controls were given water in both bottles (n=17-20 per group). Some rats from each group (n=5-6) were euthanized one week later to measure autoradiographic [H]PK-11195 binding, an indicator of microglial reactivity, and the remainder (n=11-14 per group) were tested in adulthood in 2-bottle choice, followed by nicotine self-administration using an incremental fixed ratio (FR) schedule with Sacc/EtOH and water concurrently available.

RESULTS

Isolation housing increased adolescent intake of Sacc/EtOH, but the increase did not produce an observable neuroimmunological response in brain. Adolescent EtOH exposure adult intake of both Sacc/EtOH and unsweetened EtOH, with isolate-housed rats showing a greater effect than group-housed rats. In the co-use model, a cross-price economic demand analysis revealed a substitutional relationship between Sacc/EtOH and nicotine, but no effect of adolescent Sacc/EtOH exposure. Compared to group-housed rats, isolate-housed rats were more sensitive to the changing price of nicotine and showed greater substitutability of Sacc/EtOH for nicotine.

CONCLUSION

The current results suggest that adolescent EtOH exposure , with or without isolation stress, does not likely explain the enhanced risk for either alcohol or nicotine use later in life.

摘要

背景

青少年饮酒可能会增加成年后患物质使用障碍(SUDs)的易感性。本研究确定了青少年时期自愿摄入乙醇(EtOH)并伴有社会隔离,是否会改变成年期EtOH和尼古丁的摄入轨迹,以及是否会激活脑部神经炎症。

方法

将青春期雄性大鼠单独饲养或群居饲养,采用间歇性双瓶选择法给予0.2%糖精/20%EtOH(Sacc/EtOH)或水;对照组两瓶均给予水(每组n = 17 - 20只)。每组中的一些大鼠(n = 5 - 6只)在一周后安乐死,以测量放射自显影[H]PK - 11195结合,这是小胶质细胞反应性的指标,其余大鼠(每组n = 11 - 14只)在成年期进行双瓶选择测试,随后采用递增固定比率(FR)程序进行尼古丁自我给药,同时提供Sacc/EtOH和水。

结果

单独饲养增加了青少年对Sacc/EtOH的摄入量,但这种增加并未在大脑中产生可观察到的神经免疫反应。青少年接触EtOH会增加成年期对Sacc/EtOH和无糖EtOH的摄入量,单独饲养的大鼠比群居饲养的大鼠影响更大。在共同使用模型中,交叉价格经济需求分析显示Sacc/EtOH和尼古丁之间存在替代关系,但青少年接触Sacc/EtOH没有影响。与群居饲养的大鼠相比,单独饲养的大鼠对尼古丁价格变化更敏感,并且Sacc/EtOH对尼古丁的替代性更强。

结论

目前的结果表明,青少年接触EtOH,无论有无隔离应激,都不太可能解释其日后饮酒或吸烟风险增加的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee9/11387808/fdb8d562c979/gr1.jpg

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