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Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity
Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R) learning critically depends on the dorsal striatum (DS), spatial memory relies on the hippocampus (HPC). Strikingly, despite its potential importance for our understandi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447690/ https://www.ncbi.nlm.nih.gov/pubmed/28611691 http://dx.doi.org/10.3389/fpsyt.2017.00087 |
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author | Baudonnat, Mathieu Guillou, Jean-Louis Husson, Marianne Bohbot, Veronique D. Schwabe, Lars David, Vincent |
author_facet | Baudonnat, Mathieu Guillou, Jean-Louis Husson, Marianne Bohbot, Veronique D. Schwabe, Lars David, Vincent |
author_sort | Baudonnat, Mathieu |
collection | PubMed |
description | Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R) learning critically depends on the dorsal striatum (DS), spatial memory relies on the hippocampus (HPC). Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA) were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB) within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate) reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments. |
format | Online Article Text |
id | pubmed-5447690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54476902017-06-13 Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity Baudonnat, Mathieu Guillou, Jean-Louis Husson, Marianne Bohbot, Veronique D. Schwabe, Lars David, Vincent Front Psychiatry Psychiatry Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R) learning critically depends on the dorsal striatum (DS), spatial memory relies on the hippocampus (HPC). Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA) were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB) within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate) reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments. Frontiers Media S.A. 2017-05-30 /pmc/articles/PMC5447690/ /pubmed/28611691 http://dx.doi.org/10.3389/fpsyt.2017.00087 Text en Copyright © 2017 Baudonnat, Guillou, Husson, Bohbot, Schwabe and David. 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) or licensor 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 | Psychiatry Baudonnat, Mathieu Guillou, Jean-Louis Husson, Marianne Bohbot, Veronique D. Schwabe, Lars David, Vincent Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity |
title | Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity |
title_full | Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity |
title_fullStr | Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity |
title_full_unstemmed | Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity |
title_short | Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity |
title_sort | morphine reward promotes cue-sensitive learning: implication of dorsal striatal creb activity |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447690/ https://www.ncbi.nlm.nih.gov/pubmed/28611691 http://dx.doi.org/10.3389/fpsyt.2017.00087 |
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