ArticleNeuroscience2013
Opiate-induced changes in brain adenosine levels and narcotic drug responses.
Article in Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Metabolomic analysis of plasma and brain tissues in fentanyl-induced conditioned place preference mice.Frontiers in pharmacology · 2026Article
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Dysregulated Lipid Synthesis by Oncogenic IDH1 Mutation Is a Targetable Synthetic Lethal Vulnerability.Cancer discovery · 2023Article
- Opioid-Induced Reductions in Amygdala Lateral Paracapsular GABA Neuron Circuit Activity.International journal of molecular sciences · 2023Article
- Spinal AJournal of neuroscience research · 2022Article
- Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization.Nature metabolism · 2022Article
- A human multi-lineage hepatic organoid model for liver fibrosis.Nature communications · 2021Article
- Chronic Morphine-Induced Changes in Signaling at the AThe Journal of pharmacology and experimental therapeutics · 2020Article
- The phosphatidylethanolamine biosynthesis pathway provides a new target for cancer chemotherapy.Journal of hepatology · 2020Article
- Pediatric Clinical Endpoint and Pharmacodynamic Biomarkers: Limitations and Opportunities.Paediatric drugs · 2020Review
- Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017Review
- Obstructive sleep apnea, pain, and opioids: is the riddle solved?Current opinion in anaesthesiology · 2016Review
- Dynamic Regulation of the Adenosine Kinase Gene during Early Postnatal Brain Development and Maturation.Frontiers in molecular neuroscience · 2016Article
- Adenosine kinase: exploitation for therapeutic gain.Pharmacological reviews · 2013Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10-40 mg/kg) administered over a 4-day period selectively induced a twofold decrease (p<0.00005) in adenosine abundance in the brainstem of C57BL/6 mice, which exhibited symptoms of narcotic drug dependence; but did not decrease adenosine abundance in 129Sv1 mice, which do not exhibit symptoms of dependence. Based on this finding, the effect of adenosine on dependence was investigated in genetically engineered mice with alterations in adenosine tone in the brain and in pharmacologic experiments. Morphine withdrawal behaviors were significantly diminished (p<0.0004) in genetically engineered mice with reduced adenosine tone in the brainstem, and by treatment with an adenosine receptor(1) (A(1)) agonist (2-chloro-N6-cyclopentyladenosine, 0.5mg/kg) or an A(2a) receptor (A(2a)) antagonist (SCH 58261, 1mg/kg). These results indicate that adenosine homeostasis plays a crucial role in narcotic drug responses. Opiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal.
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Registered trials
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