ArticleMolecular psychiatry2015
The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Metabotropic glutamate type 5 receptor binding availability during dextroamphetamine sensitization in mice and humans.Journal of psychiatry & neuroscience : JPN · 2021Trial
- Phenotypic Behavioural Effects of Genetic Deletion of the Vesicular Glutamate Transporter 3 in 5-Hydroxytryptamine Neurons.Genes, brain, and behavior · 2026Article
- Synaptic Targets and Cellular Sources of CB1 Cannabinoid Receptor and Vesicular Glutamate Transporter-3 Expressing Nerve Terminals in Relation to GABAergic Neurons in the Human Cerebral Cortex.The European journal of neuroscience · 2025Article
- Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders.Cell reports · 2024Article
- The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice.Nature communications · 2024Article
- VGLUT3 Deletion Rescues Motor Deficits and Neuronal Loss in the zQ175 Mouse Model of Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Continuous cholinergic-dopaminergic updating in the nucleus accumbens underlies approaches to reward-predicting cues.Nature communications · 2022Article
- Functional dissociation of behavioral effects from acetylcholine and glutamate released from cholinergic striatal interneurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- A New Player in the Hippocampus: A Review on VGLUT3+ Neurons and Their Role in the Regulation of Hippocampal Activity and Behaviour.International journal of molecular sciences · 2022Review
- DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure-an explorative study.Scientific reports · 2021Article
- Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens.Communications biology · 2021Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol's dopamine-releasing effect.Addiction biology · 2021Article
- Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating.The Journal of clinical investigation · 2020Article
- Evolution of regulatory signatures in primate cortical neurons at cell-type resolution.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Brain Transcriptomics of Wild and Domestic Rabbits Suggests That Changes in Dopamine Signaling and Ciliary Function Contributed to Evolution of Tameness.Genome biology and evolution · 2020Article
- Molecular, Structural, Functional, and Pharmacological Sites for Vesicular Glutamate Transporter Regulation.Molecular neurobiology · 2020Review
- Article
- Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation.Molecular brain · 2019Article
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Authors and funding
27 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulation of reward and addiction are still unknown. In this study, we showed that disruption of the gene that encodes VGLUT3 (Slc17a8) markedly increased cocaine self-administration in mice. Concomitantly, the amount of dopamine (DA) release was strongly augmented in the NAc of VGLUT3(-/-) mice because of a lack of signaling by metabotropic glutamate receptors. Furthermore, dendritic spines and glutamatergic synaptic transmission on medium spiny neurons were increased in the NAc of VGLUT3(-/-) mice. Increased DA and glutamate signaling in the NAc are hallmarks of addiction. Our study shows that TANs use glutamate to reduce DA release and decrease reinforcing properties of cocaine in mice. Interestingly, we also observed an increased frequency of rare variations in SLC17A8 in a cohort of severe drug abusers compared with controls. Our findings identify VGLUT3 as an unexpected regulator of drug abuse.
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