Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice
BackgroundAlcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute w...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1143720/full |
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| author | Simone Tonetto Simone Tonetto Simone Tonetto Pia Weikop Tomasz Brudek Tomasz Brudek Morgane Thomsen Morgane Thomsen Morgane Thomsen |
| author_facet | Simone Tonetto Simone Tonetto Simone Tonetto Pia Weikop Tomasz Brudek Tomasz Brudek Morgane Thomsen Morgane Thomsen Morgane Thomsen |
| author_sort | Simone Tonetto |
| collection | DOAJ |
| description | BackgroundAlcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure.MethodsFemale C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC).ResultsBoth C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover.ConclusionOur findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients. |
| first_indexed | 2024-04-10T07:45:26Z |
| format | Article |
| id | doaj.art-5ccb12d54ea24bc6a28d887c49ec8b02 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-10T07:45:26Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-5ccb12d54ea24bc6a28d887c49ec8b022023-02-23T10:48:39ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532023-02-011710.3389/fnbeh.2023.11437201143720Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj miceSimone Tonetto0Simone Tonetto1Simone Tonetto2Pia Weikop3Tomasz Brudek4Tomasz Brudek5Morgane Thomsen6Morgane Thomsen7Morgane Thomsen8Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen, University Hospital of Copenhagen, Copenhagen, DenmarkCopenhagen Center for Translational Research, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCenter for Translational Neuromedicine, University of Copenhagen, Copenhagen, DenmarkCopenhagen Center for Translational Research, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkResearch Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkLaboratory of Neuropsychiatry, Psychiatric Center Copenhagen, University Hospital of Copenhagen, Copenhagen, DenmarkCopenhagen Center for Translational Research, Bispebjerg-Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, DenmarkDepartment of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkBackgroundAlcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure.MethodsFemale C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC).ResultsBoth C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover.ConclusionOur findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients.https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1143720/fullalcohol withdrawalmouse strainsbehavioral testsHPLCneuroinflammation |
| spellingShingle | Simone Tonetto Simone Tonetto Simone Tonetto Pia Weikop Tomasz Brudek Tomasz Brudek Morgane Thomsen Morgane Thomsen Morgane Thomsen Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice Frontiers in Behavioral Neuroscience alcohol withdrawal mouse strains behavioral tests HPLC neuroinflammation |
| title | Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice |
| title_full | Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice |
| title_fullStr | Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice |
| title_full_unstemmed | Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice |
| title_short | Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice |
| title_sort | behavioral and biochemical effects of alcohol withdrawal in female c3h henrj and c57bl 6jrj mice |
| topic | alcohol withdrawal mouse strains behavioral tests HPLC neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1143720/full |
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