Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure
Abstract Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-80767-7 |
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| author | Carole Morel Lyonna F. Parise Yentl Y. Van der Zee Orna Issler Min Cai Caleb J. Browne Anthony Blando Katherine B. LeClair Antonio V. Aubry Sherod Haynes Robert W. Williams Megan K. Mulligan Scott J. Russo Eric J. Nestler Ming-Hu Han |
| author_facet | Carole Morel Lyonna F. Parise Yentl Y. Van der Zee Orna Issler Min Cai Caleb J. Browne Anthony Blando Katherine B. LeClair Antonio V. Aubry Sherod Haynes Robert W. Williams Megan K. Mulligan Scott J. Russo Eric J. Nestler Ming-Hu Han |
| author_sort | Carole Morel |
| collection | DOAJ |
| description | Abstract Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions—specifically gene x chronic stress—here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J. Utilizing the chronic social defeat stress (CSDS) and chronic variable stress (CVS) paradigms, we first showed sexual dimorphism in social and exploratory behaviors between the mouse strains. Further, we observed an interaction between genetic background and vulnerability to prolonged exposure to non-social stressors. Finally, we found that DBA/2J and C57BL/6J mice pre-exposed to stress displayed differences in morphine sensitivity. Our results support the hypothesis that genetic variation influences chronic stress-induced behavioral outcomes such as social and approach-avoidance behaviors, reward responses, as well as morphine sensitivity, and is likely to modulate the development of drug addiction. |
| format | Article |
| id | doaj-art-207efff159214bad9dc045ff45b7f249 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-207efff159214bad9dc045ff45b7f2492025-08-20T02:43:25ZengNature PortfolioScientific Reports2045-23222024-12-0114111210.1038/s41598-024-80767-7Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposureCarole Morel0Lyonna F. Parise1Yentl Y. Van der Zee2Orna Issler3Min Cai4Caleb J. Browne5Anthony Blando6Katherine B. LeClair7Antonio V. Aubry8Sherod Haynes9Robert W. Williams10Megan K. Mulligan11Scott J. Russo12Eric J. Nestler13Ming-Hu Han14Department of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science CenterDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science CenterFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiFriedman Brain Institute, and Center for Affective Neuroscience, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiAbstract Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions—specifically gene x chronic stress—here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J. Utilizing the chronic social defeat stress (CSDS) and chronic variable stress (CVS) paradigms, we first showed sexual dimorphism in social and exploratory behaviors between the mouse strains. Further, we observed an interaction between genetic background and vulnerability to prolonged exposure to non-social stressors. Finally, we found that DBA/2J and C57BL/6J mice pre-exposed to stress displayed differences in morphine sensitivity. Our results support the hypothesis that genetic variation influences chronic stress-induced behavioral outcomes such as social and approach-avoidance behaviors, reward responses, as well as morphine sensitivity, and is likely to modulate the development of drug addiction.https://doi.org/10.1038/s41598-024-80767-7 |
| spellingShingle | Carole Morel Lyonna F. Parise Yentl Y. Van der Zee Orna Issler Min Cai Caleb J. Browne Anthony Blando Katherine B. LeClair Antonio V. Aubry Sherod Haynes Robert W. Williams Megan K. Mulligan Scott J. Russo Eric J. Nestler Ming-Hu Han Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure Scientific Reports |
| title | Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure |
| title_full | Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure |
| title_fullStr | Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure |
| title_full_unstemmed | Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure |
| title_short | Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure |
| title_sort | male and female behavioral variability and morphine response in c57bl 6j dba 2j and their bxd progeny following chronic stress exposure |
| url | https://doi.org/10.1038/s41598-024-80767-7 |
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