Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior
Summary: The nucleus accumbens (NAc) plays a key role in drug-related behavior and natural reward learning. Synaptic plasticity in dopamine D1 and D2 receptor medium spiny neurons (MSNs) of the NAc and the endogenous cannabinoid (eCB) system have been implicated in reward seeking. However, the preci...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-03-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220301358 |
| _version_ | 1818145590972776448 |
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| author | Ainhoa Bilbao Daniela Neuhofer Marja Sepers Shou-peng Wei Manuela Eisenhardt Sarah Hertle Olivier Lassalle Almudena Ramos-Uriarte Nagore Puente Raissa Lerner Aurore Thomazeau Pedro Grandes Beat Lutz Olivier J. Manzoni Rainer Spanagel |
| author_facet | Ainhoa Bilbao Daniela Neuhofer Marja Sepers Shou-peng Wei Manuela Eisenhardt Sarah Hertle Olivier Lassalle Almudena Ramos-Uriarte Nagore Puente Raissa Lerner Aurore Thomazeau Pedro Grandes Beat Lutz Olivier J. Manzoni Rainer Spanagel |
| author_sort | Ainhoa Bilbao |
| collection | DOAJ |
| description | Summary: The nucleus accumbens (NAc) plays a key role in drug-related behavior and natural reward learning. Synaptic plasticity in dopamine D1 and D2 receptor medium spiny neurons (MSNs) of the NAc and the endogenous cannabinoid (eCB) system have been implicated in reward seeking. However, the precise molecular and physiological basis of reward-seeking behavior remains unknown. We found that the specific deletion of metabotropic glutamate receptor 5 (mGluR5) in D1-expressing MSNs (D1miRmGluR5 mice) abolishes eCB-mediated long-term depression (LTD) and prevents the expression of drug (cocaine and ethanol), natural reward (saccharin), and brain-stimulation-seeking behavior. In vivo enhancement of 2-arachidonoylglycerol (2-AG) eCB signaling within the NAc core restores both eCB-LTD and reward-seeking behavior in D1miRmGluR5 mice. The data suggest a model where the eCB and glutamatergic systems of the NAc act in concert to mediate reward-seeking responses. : Neuroscience; Behavioral Neuroscience; Molecular Neuroscience Subject Areas: Neuroscience, Behavioral Neuroscience, Molecular Neuroscience |
| first_indexed | 2024-12-11T12:05:53Z |
| format | Article |
| id | doaj.art-2cbad26abe8c4107aca367289fd27f7d |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-11T12:05:53Z |
| publishDate | 2020-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-2cbad26abe8c4107aca367289fd27f7d2022-12-22T01:07:56ZengElsevieriScience2589-00422020-03-01233Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking BehaviorAinhoa Bilbao0Daniela Neuhofer1Marja Sepers2Shou-peng Wei3Manuela Eisenhardt4Sarah Hertle5Olivier Lassalle6Almudena Ramos-Uriarte7Nagore Puente8Raissa Lerner9Aurore Thomazeau10Pedro Grandes11Beat Lutz12Olivier J. Manzoni13Rainer Spanagel14Behavioral Genetics Research Group, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, Germany; Corresponding authorINSERM U1249, Parc Scientifique de Luminy - BP 13 - 13273, Marseille Cedex 09, France; Aix-Marseille University, Jardindu Pharo, 58 Boulevard Charles Livon, Marseille, 13007, FranceINSERM U1249, Parc Scientifique de Luminy - BP 13 - 13273, Marseille Cedex 09, France; Aix-Marseille University, Jardindu Pharo, 58 Boulevard Charles Livon, Marseille, 13007, FranceBehavioral Genetics Research Group, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, GermanyBehavioral Genetics Research Group, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, GermanyBehavioral Genetics Research Group, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, GermanyINSERM U1249, Parc Scientifique de Luminy - BP 13 - 13273, Marseille Cedex 09, France; Aix-Marseille University, Jardindu Pharo, 58 Boulevard Charles Livon, Marseille, 13007, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, INSERM-Indiana University, 107 S Indiana Avenue, Bloomington, IN 47405, USADepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, Spain; Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, SpainDepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, Spain; Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, SpainInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg, University Mainz, Duesbergweg 6, 55099 Mainz, GermanyINSERM U1249, Parc Scientifique de Luminy - BP 13 - 13273, Marseille Cedex 09, France; Aix-Marseille University, Jardindu Pharo, 58 Boulevard Charles Livon, Marseille, 13007, FranceDepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, Spain; Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, SpainInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg, University Mainz, Duesbergweg 6, 55099 Mainz, GermanyINSERM U1249, Parc Scientifique de Luminy - BP 13 - 13273, Marseille Cedex 09, France; Aix-Marseille University, Jardindu Pharo, 58 Boulevard Charles Livon, Marseille, 13007, France; Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, INSERM-Indiana University, 107 S Indiana Avenue, Bloomington, IN 47405, USA; Corresponding authorInstitute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Medical Faculty Mannheim, 68159 Mannheim, Germany; Corresponding authorSummary: The nucleus accumbens (NAc) plays a key role in drug-related behavior and natural reward learning. Synaptic plasticity in dopamine D1 and D2 receptor medium spiny neurons (MSNs) of the NAc and the endogenous cannabinoid (eCB) system have been implicated in reward seeking. However, the precise molecular and physiological basis of reward-seeking behavior remains unknown. We found that the specific deletion of metabotropic glutamate receptor 5 (mGluR5) in D1-expressing MSNs (D1miRmGluR5 mice) abolishes eCB-mediated long-term depression (LTD) and prevents the expression of drug (cocaine and ethanol), natural reward (saccharin), and brain-stimulation-seeking behavior. In vivo enhancement of 2-arachidonoylglycerol (2-AG) eCB signaling within the NAc core restores both eCB-LTD and reward-seeking behavior in D1miRmGluR5 mice. The data suggest a model where the eCB and glutamatergic systems of the NAc act in concert to mediate reward-seeking responses. : Neuroscience; Behavioral Neuroscience; Molecular Neuroscience Subject Areas: Neuroscience, Behavioral Neuroscience, Molecular Neurosciencehttp://www.sciencedirect.com/science/article/pii/S2589004220301358 |
| spellingShingle | Ainhoa Bilbao Daniela Neuhofer Marja Sepers Shou-peng Wei Manuela Eisenhardt Sarah Hertle Olivier Lassalle Almudena Ramos-Uriarte Nagore Puente Raissa Lerner Aurore Thomazeau Pedro Grandes Beat Lutz Olivier J. Manzoni Rainer Spanagel Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior iScience |
| title | Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior |
| title_full | Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior |
| title_fullStr | Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior |
| title_full_unstemmed | Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior |
| title_short | Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior |
| title_sort | endocannabinoid ltd in accumbal d1 neurons mediates reward seeking behavior |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220301358 |
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