Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice
Patients suffering from opioid use disorder often relapse during periods of abstinence, which is posited to be caused by negative affective states that drive motivated behaviors. Here, we explored whether conditioning mice with morphine in a conditioned place preference (CPP) training paradigm evoke...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnbeh.2020.00075/full |
| _version_ | 1818963908846682112 |
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| author | Greer McKendrick Greer McKendrick Hannah Garrett Holly E. Jones Holly E. Jones Dillon S. McDevitt Dillon S. McDevitt Sonakshi Sharma Yuval Silberman Nicholas M. Graziane |
| author_facet | Greer McKendrick Greer McKendrick Hannah Garrett Holly E. Jones Holly E. Jones Dillon S. McDevitt Dillon S. McDevitt Sonakshi Sharma Yuval Silberman Nicholas M. Graziane |
| author_sort | Greer McKendrick |
| collection | DOAJ |
| description | Patients suffering from opioid use disorder often relapse during periods of abstinence, which is posited to be caused by negative affective states that drive motivated behaviors. Here, we explored whether conditioning mice with morphine in a conditioned place preference (CPP) training paradigm evoked anxiety-like behavior during morphine abstinence. To do this, mice were conditioned with morphine (10 mg/kg, i.p.) for 5 days. Twenty-four hours following conditioning, anxiety levels were tested by measuring time in the open arms of the elevated plus-maze. The next day, mice were placed in the three-compartment chamber to measure morphine-induced CPP. Our results show that following morphine conditioning, mice spent significantly less time in the open arm of the elevated plus-maze and expressed robust morphine CPP on CPP test day. Furthermore, we found that an acute treatment with (R,S)-ketamine (10 mg/kg, i.p.), a medication demonstrating promise for preventing anxiety-related phenotypes, 30 min before testing on post-conditioning day 1, increased time spent in the open arm of the elevated plus-maze in saline- and morphine-conditioned mice. Additionally, we found that the second injection of ketamine 30 min before CPP tests on post-conditioning day 2 prevented morphine-induced CPP, which lasted for up to 28 days post-conditioning. Furthermore, we found that conditioning mice with 10% (w/v) sucrose using an oral self-administration procedure did not evoke anxiety-like behavior, but elicited robust CPP, which was attenuated by ketamine treatment 30 min before CPP tests. Overall, our results suggest that the ketamine-induced block of morphine CPP may not be attributed solely to alleviating negative affective states, but potentially through impaired memory of morphine-context associations. |
| first_indexed | 2024-12-20T12:52:42Z |
| format | Article |
| id | doaj.art-a14a8ae4988f4a39812a0afd5f8ad1f4 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-20T12:52:42Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-a14a8ae4988f4a39812a0afd5f8ad1f42022-12-21T19:40:09ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532020-05-011410.3389/fnbeh.2020.00075525531Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in MiceGreer McKendrick0Greer McKendrick1Hannah Garrett2Holly E. Jones3Holly E. Jones4Dillon S. McDevitt5Dillon S. McDevitt6Sonakshi Sharma7Yuval Silberman8Nicholas M. Graziane9Neuroscience Graduate Program, Penn State College of Medicine, Hershey, PA, United StatesDepartment of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA, United StatesDepartment of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA, United StatesDepartment of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA, United StatesSummer Undergraduate Research Internship Program, Penn State College of Medicine, Hershey, PA, United StatesNeuroscience Graduate Program, Penn State College of Medicine, Hershey, PA, United StatesSummer Undergraduate Research Internship Program, Penn State College of Medicine, Hershey, PA, United StatesDepartment of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA, United StatesDepartment of Neural and Behavioral Sciences, Penn State College of Medicine, Pennsylvania State University, Hershey, PA, United StatesDepartments of Anesthesiology and Perioperative Medicine and Pharmacology, Penn State College of Medicine, Hershey, PA, United StatesPatients suffering from opioid use disorder often relapse during periods of abstinence, which is posited to be caused by negative affective states that drive motivated behaviors. Here, we explored whether conditioning mice with morphine in a conditioned place preference (CPP) training paradigm evoked anxiety-like behavior during morphine abstinence. To do this, mice were conditioned with morphine (10 mg/kg, i.p.) for 5 days. Twenty-four hours following conditioning, anxiety levels were tested by measuring time in the open arms of the elevated plus-maze. The next day, mice were placed in the three-compartment chamber to measure morphine-induced CPP. Our results show that following morphine conditioning, mice spent significantly less time in the open arm of the elevated plus-maze and expressed robust morphine CPP on CPP test day. Furthermore, we found that an acute treatment with (R,S)-ketamine (10 mg/kg, i.p.), a medication demonstrating promise for preventing anxiety-related phenotypes, 30 min before testing on post-conditioning day 1, increased time spent in the open arm of the elevated plus-maze in saline- and morphine-conditioned mice. Additionally, we found that the second injection of ketamine 30 min before CPP tests on post-conditioning day 2 prevented morphine-induced CPP, which lasted for up to 28 days post-conditioning. Furthermore, we found that conditioning mice with 10% (w/v) sucrose using an oral self-administration procedure did not evoke anxiety-like behavior, but elicited robust CPP, which was attenuated by ketamine treatment 30 min before CPP tests. Overall, our results suggest that the ketamine-induced block of morphine CPP may not be attributed solely to alleviating negative affective states, but potentially through impaired memory of morphine-context associations.https://www.frontiersin.org/article/10.3389/fnbeh.2020.00075/fullnegative affectmorphineconditioned place preferenceanxietyopioid use disorderketamine |
| spellingShingle | Greer McKendrick Greer McKendrick Hannah Garrett Holly E. Jones Holly E. Jones Dillon S. McDevitt Dillon S. McDevitt Sonakshi Sharma Yuval Silberman Nicholas M. Graziane Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice Frontiers in Behavioral Neuroscience negative affect morphine conditioned place preference anxiety opioid use disorder ketamine |
| title | Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice |
| title_full | Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice |
| title_fullStr | Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice |
| title_full_unstemmed | Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice |
| title_short | Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice |
| title_sort | ketamine blocks morphine induced conditioned place preference and anxiety like behaviors in mice |
| topic | negative affect morphine conditioned place preference anxiety opioid use disorder ketamine |
| url | https://www.frontiersin.org/article/10.3389/fnbeh.2020.00075/full |
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