Heightened Exploratory Behavior Following Chronic Excessive Ethanol Drinking: Mediation by Neurotensin Receptor Type 2 in the Anterior Paraventricular Thalamus.
Heightened Exploratory Behavior Following Chronic Excessive Ethanol Drinking: Mediation by Neurotensin Receptor Type 2 in the Anterior Paraventricular Thalamus.
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DOI：
10.1111/acer.14406
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Barson JR
中科院分区：
文献类型：
--
作者：
Pandey S;Barson JR
Chronic, excessive alcohol drinkers, even without dependence, can exhibit changes in behavior and neurochemical systems. Identifying these changes and their relationship with one another could provide novel avenues for the prevention and treatment of alcohol use disorder. We recently demonstrated, in rats, that neurotensin (NTS) in the paraventricular thalamus (PVT) regulates excessive ethanol drinking. Here, we investigate the effects of chronic ethanol drinking on the PVT-NTS system and its contribution to ethanol-induced behavioral changes. We gave adult male Long-Evans rats 20% ethanol under the intermittent-access two-bottle-choice paradigm or maintained them on chow and water for up to 11 weeks. Prior to ethanol exposure and following several weeks of access, during acute abstinence, we tested these groups for multiple behaviors. In the 12th week, during acute abstinence, we examined gene expression and peptide levels of NTS and its receptors in the anterior and posterior subregions of the PVT. Finally, in chronic ethanol drinkers, during acute abstinence, we microinjected the NTS receptor type 2 (NTS2R) agonist, JMV-431, in the anterior PVT (aPVT), and examined subsequent ethanol intake and behavior. Following chronic intermittent ethanol access, rats were classified by cluster analysis as high or low ethanol drinkers. High ethanol drinkers spent more time in the light chamber of a light-dark box and open arms of an elevated plus maze and entered fewer familiar holes in a hole-board apparatus. These differences were absent prior to ethanol exposure but were detectable as early as 4 weeks into drinking. Time in the light chamber following chronic drinking also predicted level of subsequent drinking. High ethanol drinkers also showed elevated protein levels of NTS2R in the aPVT, and pharmacological stimulation of aPVT NTS2R in low drinkers mimicked the increased time spent in the light chamber that was observed in high drinkers. Our findings suggest that chronic, excessive, but not lower level, ethanol drinking induces heightened or flexible exploratory behavior, which predicts future ethanol drinking and is partly mediated by elevated NTS2R signaling in the aPVT. These ethanol-induced alterations represent adaptations that could perpetuate excessive drinking and lead to the development of ethanol dependence.
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影响因子：
4.2
作者：
Hu S;Ide JS;Chao HH;Zhornitsky S;Fischer KA;Wang W;Zhang S;Li CR
通讯作者：
Li CR
DOI：
10.1111/acer.13826
发表时间：
2018-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Gupta A;Gargiulo AT;Curtis GR;Badve PS;Pandey S;Barson JR
通讯作者：
Barson JR
影响因子：
2.5
作者：
Barson JR;Leibowitz SF
通讯作者：
Leibowitz SF
DOI：
10.1111/acer.13434
发表时间：
2017-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Kimbrough A;Kim S;Cole M;Brennan M;George O
通讯作者：
George O
影响因子：
5.3
作者：
de Guglielmo, Giordano;Crawford, Elena;George, Olivier
通讯作者：
George, Olivier