Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication
Alcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important f...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/11/2/189 |
| _version_ | 1797415012835262464 |
|---|---|
| author | Bryan E. Jensen Kayla G. Townsley Kolter B. Grigsby Pamela Metten Meher Chand Miracle Uzoekwe Alex Tran Evan Firsick Katherine LeBlanc John C. Crabbe Angela R. Ozburn |
| author_facet | Bryan E. Jensen Kayla G. Townsley Kolter B. Grigsby Pamela Metten Meher Chand Miracle Uzoekwe Alex Tran Evan Firsick Katherine LeBlanc John C. Crabbe Angela R. Ozburn |
| author_sort | Bryan E. Jensen |
| collection | DOAJ |
| description | Alcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important for identifying treatment options. Here, we report on behavioral characterization of two replicate lines of mice that drink to intoxication, the High Drinking in the Dark (HDID)-1 and -2 mice, which have been selectively bred (20+ generations) for the primary phenotype of reaching high blood alcohol levels (BALs) during the drinking in the dark (DID) task, a binge-like drinking assay. Along with their genetically heterogenous progenitor line, Hs/Npt, we tested these mice on: DID and drinking in the light (DIL); temporal drinking patterns; ethanol sensitivity, through loss of righting reflex (LORR); and operant self-administration, including fixed ratio (FR1), fixed ratio 3:1 (FR3), extinction/reinstatement, and progressive ratio (PR). All mice consumed more ethanol during the dark than the light and both HDID lines consumed more ethanol than Hs/Npt during DIL and DID. In the dark, we found that the HDID lines achieved high blood alcohol levels early into a drinking session, suggesting that they exhibit front loading like drinking behavior in the absence of the chronicity usually required for such behavior. Surprisingly, HDID-1 (female and male) and HDID-2 (male) mice were more sensitive to the intoxicating effects of ethanol during the dark (as determined by LORR), while Hs/Npt (female and male) and HDID-2 (female) mice appeared less sensitive. We observed lower HDID-1 ethanol intake compared to either HDID-2 or Hs/Npt during operant ethanol self-administration. There were no genotype differences for either progressive ratio responding, or cue-induced ethanol reinstatement, though the latter is complicated by a lack of extinguished responding behavior. Taken together, these findings suggest that genes affecting one AUD-related behavior do not necessarily affect other AUD-related behaviors. Moreover, these findings highlight that alcohol-related behaviors can also differ between lines selectively bred for the same phenotype, and even between sexes within those same line. |
| first_indexed | 2024-03-09T05:41:56Z |
| format | Article |
| id | doaj.art-277bd0ad10ee40c9a3f55b6c4536e17b |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-09T05:41:56Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-277bd0ad10ee40c9a3f55b6c4536e17b2023-12-03T12:24:06ZengMDPI AGBrain Sciences2076-34252021-02-0111218910.3390/brainsci11020189Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to IntoxicationBryan E. Jensen0Kayla G. Townsley1Kolter B. Grigsby2Pamela Metten3Meher Chand4Miracle Uzoekwe5Alex Tran6Evan Firsick7Katherine LeBlanc8John C. Crabbe9Angela R. Ozburn10Department of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USADepartment of Behavioral Neuroscience, Oregon Health & Science University, and VA Portland Health Care System, Portland, OR 97239, USAAlcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important for identifying treatment options. Here, we report on behavioral characterization of two replicate lines of mice that drink to intoxication, the High Drinking in the Dark (HDID)-1 and -2 mice, which have been selectively bred (20+ generations) for the primary phenotype of reaching high blood alcohol levels (BALs) during the drinking in the dark (DID) task, a binge-like drinking assay. Along with their genetically heterogenous progenitor line, Hs/Npt, we tested these mice on: DID and drinking in the light (DIL); temporal drinking patterns; ethanol sensitivity, through loss of righting reflex (LORR); and operant self-administration, including fixed ratio (FR1), fixed ratio 3:1 (FR3), extinction/reinstatement, and progressive ratio (PR). All mice consumed more ethanol during the dark than the light and both HDID lines consumed more ethanol than Hs/Npt during DIL and DID. In the dark, we found that the HDID lines achieved high blood alcohol levels early into a drinking session, suggesting that they exhibit front loading like drinking behavior in the absence of the chronicity usually required for such behavior. Surprisingly, HDID-1 (female and male) and HDID-2 (male) mice were more sensitive to the intoxicating effects of ethanol during the dark (as determined by LORR), while Hs/Npt (female and male) and HDID-2 (female) mice appeared less sensitive. We observed lower HDID-1 ethanol intake compared to either HDID-2 or Hs/Npt during operant ethanol self-administration. There were no genotype differences for either progressive ratio responding, or cue-induced ethanol reinstatement, though the latter is complicated by a lack of extinguished responding behavior. Taken together, these findings suggest that genes affecting one AUD-related behavior do not necessarily affect other AUD-related behaviors. Moreover, these findings highlight that alcohol-related behaviors can also differ between lines selectively bred for the same phenotype, and even between sexes within those same line.https://www.mdpi.com/2076-3425/11/2/189micedrinking in the darkselected linesoperant self-administrationethanolsensitivity to ethanol |
| spellingShingle | Bryan E. Jensen Kayla G. Townsley Kolter B. Grigsby Pamela Metten Meher Chand Miracle Uzoekwe Alex Tran Evan Firsick Katherine LeBlanc John C. Crabbe Angela R. Ozburn Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication Brain Sciences mice drinking in the dark selected lines operant self-administration ethanol sensitivity to ethanol |
| title | Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication |
| title_full | Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication |
| title_fullStr | Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication |
| title_full_unstemmed | Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication |
| title_short | Ethanol-Related Behaviors in Mouse Lines Selectively Bred for Drinking to Intoxication |
| title_sort | ethanol related behaviors in mouse lines selectively bred for drinking to intoxication |
| topic | mice drinking in the dark selected lines operant self-administration ethanol sensitivity to ethanol |
| url | https://www.mdpi.com/2076-3425/11/2/189 |
| work_keys_str_mv | AT bryanejensen ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT kaylagtownsley ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT kolterbgrigsby ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT pamelametten ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT meherchand ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT miracleuzoekwe ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT alextran ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT evanfirsick ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT katherineleblanc ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT johnccrabbe ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication AT angelarozburn ethanolrelatedbehaviorsinmouselinesselectivelybredfordrinkingtointoxication |