Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior

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Date
2020-03-27
Author
Bilbao, Ainhoa
Neuhofer, Daniela
Sepers, Marja
Wei, Shou-peng
Eisenhardt, Manuela
Hertle, Sarah
Lassalle, Olivier
Ramos Uriarte, Almudena ORCID
Puente Bustinza, Nagore ORCID
Lerner, Raissa
Thomazeau, Aurore
Grandes Moreno, Pedro Rolando ORCID
Lutz, Beat
Manzoni, Olivier J.
Spanagel, Rainer
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iScience 23(3) : (2020) // Article ID UNSP 100951
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http://hdl.handle.net/10810/44121
Abstract
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 (D1(miR)m-GluR5 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 D1-(miR)mGluR5 mice. The data suggest a model where the eCB and glutamatergic systems of the NAc act in concert to mediate reward-seeking responses.
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2020 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as 2020 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/