ReviewCNS & neurological disorders drug targets2015
Targeting the Toll of Drug Abuse: The Translational Potential of Toll-Like Receptor 4.
Review in CNS & neurological disorders drug targets, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 90 citations in OpenAlex.
- Salivary transcriptomic study to understand the molecular effects of feeding dysregulation in opioid-exposed neonates born late preterm.Journal of neonatal-perinatal medicine · 2026Observational
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Morphine and methamphetamine trigger divergent post-transcriptional neuroimmune landscapes in the dorsal striatum.bioRxiv : the preprint server for biology · 2026Article
- The effect of neuroimmune signalling on drug addiction.Frontiers in pharmacology · 2026Review
- The Role of Toll-like Receptor 3 Signaling in Cognitive Impairment Induced by Propofol Addiction.Molecular neurobiology · 2025Article
- Abstinence from cocaine self-administration promotes microglial pruning of astrocytes, which drives cocaine-seeking behavior.Cell reports · 2025Article
- Therapeutic targeting of neuroinflammation in methamphetamine use disorder.Future medicinal chemistry · 2025Review
- Real-time monitoring with iTLR4 assay identifies ligand-dependent TLR4-TLR4 conformational dynamics.Frontiers in immunology · 2025Article
- Human IPSC-Derived PreBötC-Like Neurons and Development of an Opiate Overdose and Recovery Model.Advanced biology · 2024Article
- The influence of drug class on reward in substance use disorders.Pharmacology, biochemistry, and behavior · 2024Review
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
- Fentanyl enhances immune cell response through TLR4/MD-2 complex.Frontiers in pharmacology · 2024Article
- Opioid trail: Tracking contributions to opioid use disorder from host genetics to the gut microbiome.Neuroscience and biobehavioral reviews · 2024Review
- The Magic Methyl and Its Tricks in Drug Discovery and Development.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Transcriptional and epigenetic regulation of microglia in substance use disorders.Molecular and cellular neurosciences · 2023Review
- Cyanidin prevents MDPV withdrawal-induced anxiety-like effects and dysregulation of cytokine systems in rats.Brain research · 2023Article
- Sex-specific inflammatory and white matter effects of prenatal opioid exposure: a pilot study.Pediatric research · 2023Article
- Cognitive impairment and changes of red blood cell components and serum levels of IL-6, IL-18, and L-tryptophan in methamphetamine abusers.American journal of neurodegenerative disease · 2023Article
- Opioid use disorder: current trends and potential treatments.Frontiers in public health · 2023Review
- Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors.Translational psychiatry · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
There is growing recognition that glial proinflammatory activation importantly contributes to the rewarding and reinforcing effects of a variety of drugs of abuse, including cocaine, methamphetamine, opioids, and alcohol. It has recently been proposed that glia are recognizing, and becoming activated by, such drugs as a CNS immunological response to these agents being xenobiotics; that is, substances foreign to the brain. Activation of glia, primarily microglia, by various drugs of abuse occurs via toll like receptor 4 (TLR4). The detection of such xenobiotics by TLR4 results in the release of glial neuroexcitatory and neurotoxic substances. These glial products of TLR4 activation enhance neuronal excitability within brain reward circuitry, thereby enhancing their rewarding and reinforcing effects. Indeed, selective pharmacological blockade of TLR4 activation, such as with the non-opioid TLR4 antagonist (+)-naltrexone, suppresses a number of indices of drug reward/reinforcement. These include: conditioned place preference, self-administration, drugprimed reinstatement, incubation of craving, and elevations of nucleus accumbens shell dopamine. Notably, TLR4 blockade fails to alter self-administration of food, indicative of a selective effect on drugs of abuse. Genetic disruption of TLR4 signaling recapitulates the effects of pharmacological TLR4 blockade, providing converging lines of evidence of a central importance of TLR4. Taken together, multiple lines of evidence converge to raise TLR4 as a promising therapeutic target for drug abuse.
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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.