ArticleNature communications2023
Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- BDNF restores impaired long-term potentiation of GABAergic synapses induced by chronic ethanol exposure in the VTA and attenuates reward-seeking behavior.Molecular psychiatry · 2026Article
- Midbrain endocannabinoids actuate dopamine-based action selection.Cell reports · 2026Article
- Distribution and subacute modulation of endocannabinoid metabolizing enzymes in the trigeminal complex and midbrain in a pre-clinical model of post-traumatic headache.The journal of headache and pain · 2026Article
- Cannabinoid-based Pharmacology for the Management of Substance Use Disorders.Current topics in behavioral neurosciences · 2026Review
- FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- The dopaminergic system in neurodevelopment: preclinical models of neurodevelopmental disorders and susceptibility to neurodegeneration.Frontiers in cellular neuroscience · 2026Review
- Distinct serum endocannabinoid profiles in treatment-naïve Han Chinese children with ADHD: a case-control pilot study.Frontiers in neurology · 2025Article
- ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice.Nature communications · 2024Article
- Beyond dopamine: exploring endocannabinoids in Parkinson's disease.Ageing and neurodegenerative diseases · 2024Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice. We find that DGLα deletion from VTA dopamine neurons prevents depolarization-induced suppression of excitation (DSE), a form of 2-AG-mediated synaptic plasticity, in dopamine neurons. DGLα deletion also decreases effortful, cue-driven reward-seeking but has no effect on non-cued or low-effort operant tasks and other behaviors. Moreover, dopamine recording in the NAc reveals that deletion of DGLα impairs the transfer of accumbal dopamine signaling from a reward to its earliest predictors. These results demonstrate that 2-AG mobilization from VTA dopamine neurons is a necessary step for the generation of dopamine-based predictive associations that are required to direct and energize reward-oriented behavior.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.