Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats
With the substantial social and medical burden of addiction, there is considerable interest in understanding risk factors that increase the development of addiction. A key feature of alcohol use disorder (AUD) is compulsive alcohol (EtOH) drinking, where EtOH drinking becomes “inflexible” after chro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/12/8/1042 |
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| author | Simon N. Katner Alena M. Sentir Kevin B. Steagall Zheng-Ming Ding Leah Wetherill Frederic W. Hopf Eric A. Engleman |
| author_facet | Simon N. Katner Alena M. Sentir Kevin B. Steagall Zheng-Ming Ding Leah Wetherill Frederic W. Hopf Eric A. Engleman |
| author_sort | Simon N. Katner |
| collection | DOAJ |
| description | With the substantial social and medical burden of addiction, there is considerable interest in understanding risk factors that increase the development of addiction. A key feature of alcohol use disorder (AUD) is compulsive alcohol (EtOH) drinking, where EtOH drinking becomes “inflexible” after chronic intake, and animals, such as humans with AUD, continue drinking despite aversive consequences. Further, since there is a heritable component to AUD risk, some work has focused on genetically-selected, EtOH-preferring rodents, which could help uncover critical mechanisms driving pathological intake. In this regard, aversion-resistant drinking (ARD) takes >1 month to develop in outbred Wistar rats (and perhaps Sardinian-P EtOH-preferring rats). However, ARD has received limited study in Indiana P-rats, which were selected for high EtOH preference and exhibit factors that could parallel human AUD (including front-loading and impulsivity). Here, we show that P-rats rapidly developed compulsion-like responses for EtOH; 0.4 g/L quinine in EtOH significantly reduced female and male intake on the first day of exposure but had no effect after one week of EtOH drinking (15% EtOH, 24 h free-choice paradigm). Further, after 4–5 weeks of EtOH drinking, males but not females showed resistance to even higher quinine (0.5 g/L). Thus, P-rats rapidly developed ARD for EtOH, but only males developed even stronger ARD with further intake. Finally, rats strongly reduced intake of quinine-adulterated water after 1 or 5 weeks of EtOH drinking, suggesting no changes in basic quinine sensitivity. Thus, modeling ARD in P-rats may provide insight into mechanisms underlying genetic predispositions for compulsive drinking and lead to new treatments for AUDs. |
| first_indexed | 2024-03-09T09:59:26Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T09:59:26Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-5fe9bbeafa824c86aa02ad5d904730492023-12-01T23:31:05ZengMDPI AGBrain Sciences2076-34252022-08-01128104210.3390/brainsci12081042Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) RatsSimon N. Katner0Alena M. Sentir1Kevin B. Steagall2Zheng-Ming Ding3Leah Wetherill4Frederic W. Hopf5Eric A. Engleman6Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartments of Anesthesiology and Perioperative Medicine and Pharmacology, Pennsylvania State University College of Medicine, 700 HMC Crescent Road, Hershey, PA 17033, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAWith the substantial social and medical burden of addiction, there is considerable interest in understanding risk factors that increase the development of addiction. A key feature of alcohol use disorder (AUD) is compulsive alcohol (EtOH) drinking, where EtOH drinking becomes “inflexible” after chronic intake, and animals, such as humans with AUD, continue drinking despite aversive consequences. Further, since there is a heritable component to AUD risk, some work has focused on genetically-selected, EtOH-preferring rodents, which could help uncover critical mechanisms driving pathological intake. In this regard, aversion-resistant drinking (ARD) takes >1 month to develop in outbred Wistar rats (and perhaps Sardinian-P EtOH-preferring rats). However, ARD has received limited study in Indiana P-rats, which were selected for high EtOH preference and exhibit factors that could parallel human AUD (including front-loading and impulsivity). Here, we show that P-rats rapidly developed compulsion-like responses for EtOH; 0.4 g/L quinine in EtOH significantly reduced female and male intake on the first day of exposure but had no effect after one week of EtOH drinking (15% EtOH, 24 h free-choice paradigm). Further, after 4–5 weeks of EtOH drinking, males but not females showed resistance to even higher quinine (0.5 g/L). Thus, P-rats rapidly developed ARD for EtOH, but only males developed even stronger ARD with further intake. Finally, rats strongly reduced intake of quinine-adulterated water after 1 or 5 weeks of EtOH drinking, suggesting no changes in basic quinine sensitivity. Thus, modeling ARD in P-rats may provide insight into mechanisms underlying genetic predispositions for compulsive drinking and lead to new treatments for AUDs.https://www.mdpi.com/2076-3425/12/8/1042addictioncompulsive drinkinggenetic modelalcoholismselected linesalcohol preference |
| spellingShingle | Simon N. Katner Alena M. Sentir Kevin B. Steagall Zheng-Ming Ding Leah Wetherill Frederic W. Hopf Eric A. Engleman Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats Brain Sciences addiction compulsive drinking genetic model alcoholism selected lines alcohol preference |
| title | Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats |
| title_full | Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats |
| title_fullStr | Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats |
| title_full_unstemmed | Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats |
| title_short | Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats |
| title_sort | modeling aversion resistant alcohol intake in indiana alcohol preferring p rats |
| topic | addiction compulsive drinking genetic model alcoholism selected lines alcohol preference |
| url | https://www.mdpi.com/2076-3425/12/8/1042 |
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