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μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors

μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a se...

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Autores principales: Severino, Amie L., Mittal, Nitish, Hakimian, Joshua K., Velarde, Nathanial, Minasyan, Ani, Albert, Ralph, Torres, Carlos, Romaneschi, Nicole, Johnston, Camille, Tiwari, Suchi, Lee, Alex S., Taylor, Anna M., Gavériaux-Ruff, Claire, Kieffer, Brigitte L., Evans, Christopher J., Cahill, Catherine M., Walwyn, Wendy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508564/
https://www.ncbi.nlm.nih.gov/pubmed/32859725
http://dx.doi.org/10.1523/ENEURO.0146-20.2020
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author Severino, Amie L.
Mittal, Nitish
Hakimian, Joshua K.
Velarde, Nathanial
Minasyan, Ani
Albert, Ralph
Torres, Carlos
Romaneschi, Nicole
Johnston, Camille
Tiwari, Suchi
Lee, Alex S.
Taylor, Anna M.
Gavériaux-Ruff, Claire
Kieffer, Brigitte L.
Evans, Christopher J.
Cahill, Catherine M.
Walwyn, Wendy M.
author_facet Severino, Amie L.
Mittal, Nitish
Hakimian, Joshua K.
Velarde, Nathanial
Minasyan, Ani
Albert, Ralph
Torres, Carlos
Romaneschi, Nicole
Johnston, Camille
Tiwari, Suchi
Lee, Alex S.
Taylor, Anna M.
Gavériaux-Ruff, Claire
Kieffer, Brigitte L.
Evans, Christopher J.
Cahill, Catherine M.
Walwyn, Wendy M.
author_sort Severino, Amie L.
collection PubMed
description μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a series of genetically engineered mice based on the Cre recombinase/loxP system to selectively delete MORs from specific neurons enriched in the striatum: dopamine 1 (D1) receptors, D2 receptors, adenosine 2a (A2a) receptors, and choline acetyltransferase (ChAT). We first determined the effects of each deletion on opioid-induced locomotion, a striatal and dopamine-dependent behavior. We show that MOR deletion from D1 neurons reduced opioid (morphine and oxycodone)-induced hyperlocomotion, whereas deleting MORs from A2a neurons resulted in enhanced opioid-induced locomotion, and deleting MORs from D2 or ChAT neurons had no effect. We also present the effect of each deletion on opioid intravenous self-administration. We first assessed the acquisition of this behavior using remifentanil as the reinforcing opioid and found no effect of genotype. Mice were then transitioned to oxycodone as the reinforcer and maintained here for 9 d. Again, no genotype effect was found. However, when mice underwent 3 d of extinction training, during which the drug was not delivered, but all cues remained as during the maintenance phase, drug-seeking behavior was enhanced when MORs were deleted from A2a or ChAT neurons. These findings show that these selective MOR populations play specific roles in reward-associated behaviors.
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spelling pubmed-75085642020-09-23 μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors Severino, Amie L. Mittal, Nitish Hakimian, Joshua K. Velarde, Nathanial Minasyan, Ani Albert, Ralph Torres, Carlos Romaneschi, Nicole Johnston, Camille Tiwari, Suchi Lee, Alex S. Taylor, Anna M. Gavériaux-Ruff, Claire Kieffer, Brigitte L. Evans, Christopher J. Cahill, Catherine M. Walwyn, Wendy M. eNeuro Research Article: New Research μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a series of genetically engineered mice based on the Cre recombinase/loxP system to selectively delete MORs from specific neurons enriched in the striatum: dopamine 1 (D1) receptors, D2 receptors, adenosine 2a (A2a) receptors, and choline acetyltransferase (ChAT). We first determined the effects of each deletion on opioid-induced locomotion, a striatal and dopamine-dependent behavior. We show that MOR deletion from D1 neurons reduced opioid (morphine and oxycodone)-induced hyperlocomotion, whereas deleting MORs from A2a neurons resulted in enhanced opioid-induced locomotion, and deleting MORs from D2 or ChAT neurons had no effect. We also present the effect of each deletion on opioid intravenous self-administration. We first assessed the acquisition of this behavior using remifentanil as the reinforcing opioid and found no effect of genotype. Mice were then transitioned to oxycodone as the reinforcer and maintained here for 9 d. Again, no genotype effect was found. However, when mice underwent 3 d of extinction training, during which the drug was not delivered, but all cues remained as during the maintenance phase, drug-seeking behavior was enhanced when MORs were deleted from A2a or ChAT neurons. These findings show that these selective MOR populations play specific roles in reward-associated behaviors. Society for Neuroscience 2020-09-18 /pmc/articles/PMC7508564/ /pubmed/32859725 http://dx.doi.org/10.1523/ENEURO.0146-20.2020 Text en Copyright © 2020 Severino et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: New Research
Severino, Amie L.
Mittal, Nitish
Hakimian, Joshua K.
Velarde, Nathanial
Minasyan, Ani
Albert, Ralph
Torres, Carlos
Romaneschi, Nicole
Johnston, Camille
Tiwari, Suchi
Lee, Alex S.
Taylor, Anna M.
Gavériaux-Ruff, Claire
Kieffer, Brigitte L.
Evans, Christopher J.
Cahill, Catherine M.
Walwyn, Wendy M.
μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
title μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
title_full μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
title_fullStr μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
title_full_unstemmed μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
title_short μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors
title_sort μ-opioid receptors on distinct neuronal populations mediate different aspects of opioid reward-related behaviors
topic Research Article: New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508564/
https://www.ncbi.nlm.nih.gov/pubmed/32859725
http://dx.doi.org/10.1523/ENEURO.0146-20.2020
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