ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2011
The role of TNFα in the periaqueductal gray during naloxone-precipitated morphine withdrawal in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 74 citations in OpenAlex.
- Phospho-CREB Regulation on NMDA Glutamate Receptor 2B and Mitochondrial Calcium Uniporter in the Ventrolateral Periaqueductal Gray Controls Chronic Morphine Withdrawal in Male Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Faecal Microbiota Transplantation Modulates Morphine Addictive-Like Behaviours Through Hippocampal Metaplasticity.Addiction biology · 2025Article
- Effects of xylazine on naloxone-precipitated fentanyl withdrawal in male and female rats.Drug and alcohol dependence · 2024Article
- YTHDF1 in periaqueductal gray inhibitory neurons contributes to morphine withdrawal responses in mice.BMC medicine · 2024Article
- Tumor necrosis factor-α modulates GABAergic and dopaminergic neurons in the ventrolateral periaqueductal gray of female mice.Journal of neurophysiology · 2021Article
- The Periaqueductal Gray and Its Extended Participation in Drug Addiction Phenomena.Neuroscience bulletin · 2021Review
- The role of hippocampal glial glutamate transporter (GLT-1) in morphine-induced behavioral responses.Brain and behavior · 2021Article
- Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice.Experimental neurology · 2021Article
- Similarities in alcohol and opioid withdrawal syndromes suggest common negative reinforcement mechanisms involving the interoceptive antireward pathway.Neuroscience and biobehavioral reviews · 2021Review
- Cues conditioned to withdrawal and negative reinforcement: Neglected but key motivational elements driving opioid addiction.Science advances · 2021Review
- Glutamatergic Systems and Memory Mechanisms Underlying Opioid Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.Pharmacological reviews · 2021Review
- Melatonin Blocks Morphine-Induced Place Preference: Involvement of GLT-1, NF-κB, BDNF, and CREB in the Nucleus Accumbens.Frontiers in behavioral neuroscience · 2021Article
- Enhanced H3K4 Trimethylation in TNF-Mediators of inflammation · 2021Article
- Inhibition of NADPH oxidase within midbrain periaqueductal gray decreases pain sensitivity in Parkinson's disease via GABAergic signaling pathway.Physiological research · 2020Article
- Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice.PloS one · 2020Article
- The mitochondrial calcium uniporter contributes to morphine tolerance through pCREB and CPEB1 in rat spinal cord dorsal horn.British journal of anaesthesia · 2019Article
- TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Article
- Effects of glucosamine against morphine-induced antinociceptive tolerance and dependence in mice.Journal of biomedical science · 2019Article
- Neuronal and glial factors contributing to sex differences in opioid modulation of pain.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Tolerance and dependence are common complications of long-term treatment of pain with opioids, which substantially limit the long-term use of these drugs. The mechanisms underlying these phenomena are poorly understood. Studies have implicated the midbrain periaqueductal gray (PAG) in the pathogenesis of morphine withdrawal, and recent evidence suggests that proinflammatory cytokines in the PAG may play an important role in morphine withdrawal. Here we report that chronic morphine withdrawal-induced upregulation of glial fibrillary acidic protein (GFAP), tumor necrosis factor alpha (TNFα) and phosphorylation of ERK1/2 (pERK1/2) in the caudal ventrolateral PAG (vlPAG). Microinjection of recombinant TNFα into the vlPAG followed by intraperitoneal naloxone resulted in morphine withdrawal-like behavioral signs, and upregulation of pERK1/2, expression of Fos, and phosphorylation of cAMP response element binding (pCREB) protein. We used a herpes simplex virus (HSV)-based vector expressing p55 soluble TNF receptor (sTNFR) microinjected into the PAG to examine the role of the proinflammatory cytokine TNFα in the PAG in the naloxone-precipitated withdrawal response. Microinjection of HSV vector expressing sTNFR into the PAG before the start of morphine treatment significantly reduced the naloxone-precipitated withdrawal behavioral response and downregulated the expression of GFAP and TNFα in astrocytes of the PAG. TNFR type I colocalized with neuronal pERK1/2. Microinjection of HSV vector expressing sTNFR into the PAG also significantly reduced the phosphorylation of both ERK1/2 and CREB, and reduced Fos immunoreactivity in neurons of the PAG following naloxone-precipitated withdrawal. These results support the concept that proinflammatory cytokines expressed in astrocytes in the PAG may play an important role in the pathogenesis of morphine withdrawal response.
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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.