Chronic Augmentation of Endocannabinoid Levels Persistently Increases Dopaminergic Encoding of Reward Cost and Motivation.
dopamine
endocannabinoids
motivation
nucleus accumbens
voltammetry
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
11 08 2021
11 08 2021
Historique:
received:
05
02
2021
revised:
16
06
2021
accepted:
21
06
2021
pubmed:
8
7
2021
medline:
23
11
2021
entrez:
7
7
2021
Statut:
ppublish
Résumé
Motivational deficits characterized by an unwillingness to overcome effortful costs are a common feature of neuropsychiatric and neurologic disorders that are insufficiently understood and treated. Dopamine (DA) signaling in the nucleus accumbens (NAc) facilitates goal-seeking, but how NAc DA release encodes motivationally salient stimuli to influence effortful investment is not clear. Using fast-scan cyclic voltammetry in male and female mice, we find that NAc DA release diametrically responds to cues signaling increasing cost of reward, while DA release to the reward itself is unaffected by its cost. Because endocannabinoid (eCB) signaling facilitates goal seeking and NAc DA release, we further investigated whether repeated augmentation of the eCB 2-arachidonoylglycerol with a low dose of a monoacylglycerol lipase (MAGL) inhibitor facilitates motivation and DA signaling without the development of tolerance. We find that chronic MAGL treatment stably facilitates goal seeking and DA encoding of prior reward cost, providing critical insight into the neurobiological mechanisms of a viable treatment for motivational deficits.
Identifiants
pubmed: 34230105
pii: JNEUROSCI.0285-21.2021
doi: 10.1523/JNEUROSCI.0285-21.2021
pmc: PMC8360683
doi:
Substances chimiques
Endocannabinoids
0
Monoacylglycerol Lipases
EC 3.1.1.23
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
6946-6953Subventions
Organisme : NIDA NIH HHS
ID : R00 DA047432
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA022340
Pays : United States
Informations de copyright
Copyright © 2021 the authors.
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