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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253643/ https://www.ncbi.nlm.nih.gov/pubmed/32508606 http://dx.doi.org/10.3389/fnbeh.2020.00075 |
_version_ | 1783539372557074432 |
---|---|
author | McKendrick, Greer Garrett, Hannah Jones, Holly E. McDevitt, Dillon S. Sharma, Sonakshi Silberman, Yuval Graziane, Nicholas M. |
author_facet | McKendrick, Greer Garrett, Hannah Jones, Holly E. McDevitt, Dillon S. Sharma, Sonakshi Silberman, Yuval Graziane, Nicholas M. |
author_sort | McKendrick, Greer |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7253643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72536432020-06-05 Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice McKendrick, Greer Garrett, Hannah Jones, Holly E. McDevitt, Dillon S. Sharma, Sonakshi Silberman, Yuval Graziane, Nicholas M. Front Behav Neurosci Behavioral Neuroscience 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. Frontiers Media S.A. 2020-05-21 /pmc/articles/PMC7253643/ /pubmed/32508606 http://dx.doi.org/10.3389/fnbeh.2020.00075 Text en Copyright © 2020 McKendrick, Garrett, Jones, McDevitt, Sharma, Silberman and Graziane. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Behavioral Neuroscience McKendrick, Greer Garrett, Hannah Jones, Holly E. McDevitt, Dillon S. Sharma, Sonakshi Silberman, Yuval Graziane, Nicholas M. Ketamine Blocks Morphine-Induced Conditioned Place Preference and Anxiety-Like Behaviors in Mice |
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 | Behavioral Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253643/ https://www.ncbi.nlm.nih.gov/pubmed/32508606 http://dx.doi.org/10.3389/fnbeh.2020.00075 |
work_keys_str_mv | AT mckendrickgreer ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice AT garretthannah ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice AT joneshollye ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice AT mcdevittdillons ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice AT sharmasonakshi ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice AT silbermanyuval ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice AT grazianenicholasm ketamineblocksmorphineinducedconditionedplacepreferenceandanxietylikebehaviorsinmice |