ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Mu Opioid Receptor Modulation of Dopamine Neurons in the Periaqueductal Gray/Dorsal Raphe: A Role in Regulation of Pain.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 163 citations in OpenAlex.
- GABAergic neurons in the ventrolateral periaqueductal gray mediate fentanyl withdrawal and self-administration in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Functional Ultrasound Localization Microscopy on Freely Moving Rats.Research square · 2026Article
- Cannabidiol (CBD) modulates the serotonin-kynurenine metabolic balance in the brain of morphine-tolerant neuropathic rats.Pharmacological reports : PR · 2026Article
- Dorsal Raphe VIP Neurons Are Critical for Survival-Oriented Vigilance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Animal Models of Prenatal Opioid Exposure: Insights into Impaired Neurodevelopment.Advances in experimental medicine and biology · 2026Review
- Review
- Separable dorsal raphe dopamine projections mimic the facets of a loneliness-like state.eLife · 2025Article
- Role of astrocytic mu-opioid receptors of the ventrolateral periaqueductal gray in modulating anxiety-like responses.Behavioral and brain functions : BBF · 2025Article
- Chronic inflammatory pain and chronic THC vapor inhalation alter midbrain neuronal activity.Journal of neurophysiology · 2025Article
- Dorsal raphe GABA-ergic neurons regulate the susceptibility to social transfer of pain in mice.Acta pharmacologica Sinica · 2025Article
- Adenosine ABiological psychiatry · 2025Article
- The role of dorsal raphe nucleus neuropeptides in reward and aversion.Frontiers in behavioral neuroscience · 2025Review
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Neonatal testosterone exposure alleviates female-specific severity of formalin-induced inflammatory pain in mice.Frontiers in neural circuits · 2025Article
- Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.Science advances · 2024Article
- Role of the Dorsal Raphe Nucleus in Pain Processing.Brain sciences · 2024Review
- Article
- Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors.Addiction neuroscience · 2024Article
- The analgesic effects of insulin and its disorders in streptozotocin-induced short-term diabetes.Physiological reports · 2024Article
- An Ascending Excitatory Circuit from the Dorsal Raphe for Sensory Modulation of Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The periaqueductal gray (PAG) is a brain region involved in nociception modulation, and an important relay center for the descending nociceptive pathway through the rostral ventral lateral medulla. Given the dense expression of mu opioid receptors and the role of dopamine in pain, the recently characterized dopamine neurons in the ventral PAG (vPAG)/dorsal raphe (DR) region are a potentially critical site for the antinociceptive actions of opioids. The objectives of this study were to (1) evaluate synaptic modulation of the vPAG/DR dopamine neurons by mu opioid receptors and to (2) dissect the anatomy and neurochemistry of these neurons, in order to assess the downstream loci and functions of their activation. Using a mouse line that expresses eGFP under control of the tyrosine hydroxylase (TH) promoter, we found that mu opioid receptor activation led to a decrease in inhibitory inputs onto the vPAG/DR dopamine neurons. Furthermore, combining immunohistochemistry, optogenetics, electrophysiology, and fast-scan cyclic voltammetry in a TH-cre mouse line, we demonstrated that these neurons also express the vesicular glutamate type 2 transporter and co-release dopamine and glutamate in a major downstream projection structure-the bed nucleus of the stria terminalis. Finally, activation of TH-positive neurons in the vPAG/DR using Gq designer receptors exclusively activated by designer drugs displayed a supraspinal, but not spinal, antinociceptive effect. These results indicate that vPAG/DR dopamine neurons likely play a key role in opiate antinociception, potentially via the activation of downstream structures through dopamine and glutamate release.
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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.