ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Orexin Signaling in the VTA Gates Morphine-Induced Synaptic Plasticity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
- Chronic morphine differentially impacts glutamatergic synaptic plasticity in the ventral tegmental area of adult versus adolescent mice.Neuropharmacology · 2026Article
- Repeated Morphine Exposure Reversibly Impairs Spike Generation and Repetitive Firing in a Functionally Distinct Subpopulation of Orexin Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Review
- Peroxisome, neuropeptide, and inflammation signaling pathways uniquely impacted by opioid exposure in the hypothalamus of males and females.Molecular and cellular neurosciences · 2025Article
- Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of neuronal plasticity associated with neuropsychiatric disorders by the orexinergic system.Heliyon · 2024Review
- The Orexin/Hypocretin System, the Peptidergic Regulator of Vigilance, Orchestrates Adaptation to Stress.Biomedicines · 2024Review
- Whole Brain Mapping of Orexin Receptor mRNA Expression Visualized by Branched In Situ Hybridization Chain Reaction.eNeuro · 2024Article
- Neuropeptides Modulate Feeding via the Dopamine Reward Pathway.Neurochemical research · 2023Review
- Sex differences in VTA GABA transmission and plasticity during opioid withdrawal.Scientific reports · 2023Article
- Optogenetic and pharmacological interventions link hypocretin neurons to impulsivity in mice.Communications biology · 2023Article
- Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- The Effect of Orexin-2 and Endocannabinoid-1 Antagonists on Neuronal Activity of Hippocampal CA1 Pyramidal Neurons in Response to Tramadol in Rats.Advanced biomedical research · 2022Article
- Exploring the Role of Orexinergic Neurons in Parkinson's Disease.Neurotoxicity research · 2021Review
- Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system.Addiction biology · 2021Article
- Morphine coordinates SST and PV interneurons in the prelimbic cortex to disinhibit pyramidal neurons and enhance reward.Molecular psychiatry · 2021Article
- Drug-Evoked Synaptic Plasticity of Excitatory Transmission in the Ventral Tegmental Area.Cold Spring Harbor perspectives in medicine · 2021Review
- Glutamatergic Systems and Memory Mechanisms Underlying Opioid Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Opioid-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area Dopamine Neurons.Cold Spring Harbor perspectives in medicine · 2021Review
- Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice.Frontiers in synaptic neuroscience · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Dopamine neurons in the ventral tegmental area (VTA) are a key target of addictive drugs, and neuroplasticity in this region may underlie some of the core features of addiction. From the very first exposure, all drugs of abuse induce synaptic plasticity in the VTA. However, it is not well understood how this diverse group of drugs brings about common synaptic change. Orexin (also known as hypocretin) is a lateral hypothalamic neuropeptide released into the VTA that promotes drug-seeking behaviors and potentiates excitatory synaptic transmission onto VTA dopamine neurons. Here we show that signaling at orexin receptor type 1 (OxR1) in the VTA is required for morphine-induced plasticity of dopamine neurons. Systemic or intra-VTA administration of the OxR1 antagonist SB 334867 in rats blocked a morphine-induced increase in the AMPAR/NMDAR ratio, an increase in presynaptic glutamate release, and a postsynaptic change in AMPAR number or function, including a switch in subunit composition. Furthermore, SB 334867 blocked a morphine-induced decrease in presynaptic GABA release, and a morphine-induced shift in the balance of excitatory and inhibitory synaptic inputs to dopamine neurons. These findings identify a novel role for orexin in morphine-induced plasticity in the VTA and provide a mechanism by which orexin can gate the output of dopamine neurons.
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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.