Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior

6533b833fe1ef96bd129b7a4

RESEARCH PRODUCT

Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior

Nagore Puente Almudena Ramos-uriarte Sarah Hertle Shoupeng Wei Manuela Eisenhardt Pedro Grandes Ainhoa Bilbao Marja Sepers Marja Sepers Olivier J. Manzoni Olivier J. Manzoni Olivier J. Manzoni Olivier Lassalle Olivier Lassalle Olivier Lassalle Raissa Lerner Beat Lutz Daniela Neuhofer Daniela Neuhofer Rainer Spanagel Aurore Thomazeau Aurore Thomazeau

subject

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 Neuroscience medicine.drug

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.

year	journal	country	edition	language
2020-03-01	iScience

https://doi.org/10.1016/j.isci.2020.100951