ArticleNeurotoxicity research2002
The neurobiology of opiate tolerance, dependence and sensitization: mechanisms of NMDA receptor-dependent synaptic plasticity.
Article in Neurotoxicity research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02512055 (Ketamine Tolerance in Children After Repeated Administrations During Radiotherapy Sessions), which is not on this map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Ketamine Tolerance in Children After Repeated Administrations During Radiotherapy Sessions
Who cites it
34 citing papers in PubMed, 86 citations in OpenAlex.
- The Impact of Levetiracetam on Various Symptoms of Morphine Dependence in Mice.Life (Basel, Switzerland) · 2026Article
- The Influence of Topiramate on Morphine Dependence in Mice.Biomolecules · 2025Article
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- Role of the mesolimbic dopamine pathway in the antidepressant effects of ketamine.Neuropharmacology · 2023Review
- Risk factors for opioid use disorder after severe burns in adults.American journal of surgery · 2023Article
- Inhibition of PSD95-nNOS protein-protein interactions decreases morphine reward and relapse vulnerability in rats.Addiction biology · 2022Article
- Side Effects of Opioids Are Ameliorated by Regulating TRPV1 Receptors.International journal of environmental research and public health · 2022Review
- Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?Cellular and molecular neurobiology · 2021Review
- Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue.International journal of molecular sciences · 2020Article
- Lithium reverses the effect of opioids on eNOS/nitric oxide pathway in human umbilical vein endothelial cells.Molecular biology reports · 2020Article
- Ketamine: The final frontier or another depressing end?Behavioural brain research · 2020Review
- Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia.American journal of physiology. Endocrinology and metabolism · 2019Article
- Article
- Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration.Pharmacology, biochemistry, and behavior · 2017Article
- Antidepressant-induced Dopamine Receptor Dysregulation: A Valid Animal Model of Manic-Depressive Illness.Current neuropharmacology · 2017Review
- Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats.Iranian journal of basic medical sciences · 2015Article
- The σ1 receptor engages the redox-regulated HINT1 protein to bring opioid analgesia under NMDA receptor negative control.Antioxidants & redox signaling · 2015Article
- Memantine: New prospective in bipolar disorder treatment.World journal of psychiatry · 2014Review
- A new pharmacological role for donepezil: attenuation of morphine-induced tolerance and apoptosis in rat central nervous system.Journal of biomedical science · 2014Article
- It's MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system.Frontiers in pharmacology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-term administration of opiates leads to changes in the effects of these drugs, including tolerance, sensitization and physical dependence. There is, as yet, incomplete understanding of the neural mechanisms that underlie these phenomena. Tolerance, sensitization and physical dependence can be considered adaptive processes similar to other experience-dependent changes in the brain, such as learning and neural development. There is considerable evidence demonstrating that N-methyl-D-aspartate (NMDA) receptors and downstream signaling cascades may have an important role in different forms of experience-dependent changes in the brain and behavior. This review will explore evidence indicating that NMDA receptors and downstream messengers may be involved in opiate tolerance, sensitization and physical dependence. This evidence has been used to develop a cellular model of NMDA receptor/opiate interactions. According to this model, mu opioid receptor stimulation leads to a protein kinase C-mediated activation of NMDA receptors. Activation of NMDA receptors leads to influx of calcium and activation of calcium-dependent processes. These calcium-dependent processes have the ability to produce critical changes in opioid-responsive neurons, including inhibition of opioid receptor/second messenger coupling. This model is similar to cellular models of learning and neural development in which NMDA receptors have a central role. Together, the evidence suggests that the mechanisms that underlie changes in the brain and behavior produced by long-term opiate use may be similar to other central nervous system adaptations. The experimental findings and the resulting model may have implications for the treatment of pain and addiction.
Identifiers
What OpenQuestion holds
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.