ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2023
Ventral tegmental area glutamate neurons establish a mu-opioid receptor gated circuit to mesolimbic dopamine neurons and regulate opioid-seeking behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Opioidergic modulation of monetary incentive delay fMRI responses.Psychopharmacology · 2025Trial
- Oscillatory activity and LFP power modulation in the hippocampal CA1 and prelimbic cortex during morphine-induced place preference.IBRO neuroscience reports · 2026Article
- Acute fentanyl induces opposing directions of changes in tonic and phasic dopamine release patterns and impairs Pavlovian task performance.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Nitrous oxide controls the DCN to VTA dopamine circuit by enhancing AMPA receptor functions during rewarding behavior.Molecular psychiatry · 2026Article
- Can the incentive-sensitization theory of addiction incorporate addiction to opioid drugs?Psychopharmacology · 2026Review
- When Inhibition Fails: Adolescent Nicotine Disrupts Opioid Control of Ventral Tegmental Area GABA Neurons.Biological psychiatry · 2026Article
- VTA-forebrain connectivity moderates adaptive behavior.Brain structure & function · 2026Review
- The Role of the Ventral Tegmental Area in Reward and Addiction: A Comprehensive Review.Neurosciences (Riyadh, Saudi Arabia) · 2026Review
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- Projection-defined ventral tegmental area neurons exhibit fentanyl-induced molecular and functional adaptations that differentially support drug-context associations.bioRxiv : the preprint server for biology · 2025Article
- Crosstalk Between Glycinergic and N-Methyl-D-Aspartate Receptor-Mediated Glutamatergic Transmission in Behaviours Associated with Opioid Use Disorder.International journal of molecular sciences · 2025Review
- Untangling the multifaceted VTA responses to stress.Trends in neurosciences · 2025Review
- Salience Signaling and Stimulus Scaling of Ventral Tegmental Area Glutamate Neuron Subtypes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses.eLife · 2025Article
- VTA µ-Opioidergic Neurons Facilitate Low Sociability in Protracted Opioid Abstinence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- Untangling dopamine and glutamate in the ventral tegmental area.bioRxiv : the preprint server for biology · 2025Article
- Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses.bioRxiv : the preprint server for biology · 2025Article
- Monosynaptic ventral tegmental area glutamate projections to the locus coeruleus enhance aversive processing.bioRxiv : the preprint server for biology · 2024Article
- Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta.Addiction neuroscience · 2024Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A two-neuron model of ventral tegmental area (VTA) opioid function classically involves VTA GABA neuron regulation of VTA dopamine neurons via a mu-opioid receptor dependent inhibitory circuit. However, this model predates the discovery of a third major type of neuron in the VTA: glutamatergic neurons. We found that about one-quarter of VTA neurons expressing the mu-opioid receptor are glutamate neurons without molecular markers of GABA co-release. Glutamate-Mu opioid receptor neurons are largely distributed in the anterior VTA. The majority of remaining VTA mu-opioid receptor neurons are GABAergic neurons that are mostly within the posterior VTA and do not express molecular markers of glutamate co-release. Optogenetic stimulation of VTA glutamate neurons resulted in excitatory currents recorded from VTA dopamine neurons that were reduced by presynaptic activation of the mu-opioid receptor ex vivo, establishing a local mu-opioid receptor dependent excitatory circuit from VTA glutamate neurons to VTA dopamine neurons. This VTA glutamate to VTA dopamine pathway regulated dopamine release to the nucleus accumbens through mu-opioid receptor activity in vivo. Behaviorally, VTA glutamate calcium-related neuronal activity increased following oral oxycodone consumption during self-administration and response-contingent oxycodone-associated cues during abstinent reinstatement of drug-seeking behavior. Further, chemogenetic inhibition of VTA glutamate neurons reduced abstinent oral oxycodone-seeking behavior in male but not female mice. These results establish 1) a three-neuron model of VTA opioid function involving a mu-opioid receptor gated VTA glutamate neuron pathway to VTA dopamine neurons that controls dopamine release within the nucleus accumbens, and 2) that VTA glutamate neurons participate in opioid-seeking behavior.
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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.