Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior
| Autor: | Nagore Puente, Almudena Ramos-Uriarte, Sarah Hertle, Shoupeng Wei, Manuela Eisenhardt, Pedro Grandes, Ainhoa Bilbao, Marja Sepers, Olivier J. Manzoni, Olivier Lassalle, Raissa Lerner, Beat Lutz, Daniela Neuhofer, Rainer Spanagel, Aurore Thomazeau |
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| Přispěvatelé: | University of Heidelberg, Medical Faculty, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Johannes Gutenberg - Universität Mainz (JGU), Heidelberg University Hospital [Heidelberg], BundesministeriumfürBildung und Forschung (e:Med program, FKZ: 01ZX1311A and 01ZX1909 , Spanagel et al., 2013) and the Deutsche Forschungsgemeinschaft (DFG, Germany) TRR265/A05 and SFB1158/B04 . Work in O.J.M. laboratory is supported by INSERM . C.S. and R.L were supported by the DFG Research Unit FOR926 (central project CP1) and by the BMBF Consortium LOGIN. Funding for P.G.’s laboratory was provided by Red de TrastornosAdictivos, ISCIII (' RD16/0017/0012 ' to PG), co-funded by ERDF /ESF, 'Investing in your future', The Basque Government ( IT1230-19 ) and MINECO /FEDER, UE ( SAF2015-65034-R )., Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), pellegrino, Christophe |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
glutamate 02 engineering and technology Molecular neuroscience Biology Nucleus accumbens MGLUR5 receptors Medium spiny neuron Article induced reinstatement Behavioral Neuroscience 03 medical and health sciences Dopamine Dopamine receptor D2 lipase medicine long-term depression [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] lcsh:Science Long-term depression relapse Multidisciplinary Metabotropic glutamate receptor 5 021001 nanoscience & nanotechnology Endocannabinoid system in-vivo exposure 3. Good health rats 030104 developmental biology nervous system ethanol-seeking plasticity lcsh:Q [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Molecular Neuroscience 0210 nano-technology Neuroscience psychological phenomena and processes medicine.drug |
| Zdroj: | iScience iScience, Elsevier, 2020, 23 (3), pp.100951. ⟨10.1016/j.isci.2020.100951⟩ Addi: Archivo Digital para la Docencia y la Investigación Universidad del País Vasco iScience, Vol 23, Iss 3, Pp-(2020) Addi. Archivo Digital para la Docencia y la Investigación instname |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2020.100951 |
| Popis: | 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. Graphical Abstract Highlights • mGluR5-D1-CB1-induced eCB-LTD mediates drugs of abuse and natural reward seeking • eCB-LTD in D2-MSNs plays no important role in processing of reward-seeking responses • Loss of eCB-LTD is a consequence of higher MAGL activity and lower CB1R expression • Acute drug administration stops craving for alternative rewards on following days Neuroscience; Behavioral Neuroscience; Molecular Neuroscience |
| Databáze: | OpenAIRE |
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