Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures
Abstract
Either a single (acute) or repeated daily (chronic) injections (1 injection/day) of 20 mg/kg cocaine for 10 days to rats was found to increase reactive oxygen species production in two dopaminergic brain structures, the frontal cortex and the striatum. We found that the mitochondrial genome was down-regulated after acute cocaine injection. Hydroperoxide and lipid peroxide generation was correlated with an increase in mitochondrial hydrogen peroxide generation and with a reduced functioning of mitochondrial complex I in response to cocaine. As judged from the measurement of caspase-3 activity and TUNEL labeling, neither acute nor chronic cocaine treatment has been found to induce apoptosis in any of the structures examined. This differs dramatically from what has been described for methamphetamine. Cocaine-induced radical formation was accompanied by the induction of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, after both acute and chronic cocaine treatment. In addition, proteasome chymotrypsin-like activity was enhanced following a single cocaine injection in both cortex and striatum. It is proposed that the compensatory mechanisms to oxidative stress occurring in response to cocaine were effective in scavenging reactive oxygen species and in preventing subsequent cellular damage, thus explaining why no significant cell death was found in these brain structures.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cocaine produces oxidative stress in neurons.
“Cocaine produces oxidative stress in neurons (Dietrich et al., 2005;Numa et al., 2008;Jang et al., 2014;Sordi et al., 2014).”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Dietrich et al., 2005
Cites
1 retracted
Ghribi, O., DeWitt, D. A., Forbes, M. S., Herman, M. M., & Savory, J. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02406-4 · Cited by 94 · see citing works
RetractedIdentification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444 · see citing works
[12] Assays of glutathione peroxidase
Flohé, L., & Günzler, W. A. (1984) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(84)05015-1 · Cited by 4,954 · see citing works
Assaying for superoxide dismutase activity: Some large consequences of minor changes in conditions
Beyer, W. F., & Fridovich, I. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90489-1 · Cited by 2,925 · see citing works
Mitochondrial Complex I Deficiency in Parkinson's Disease
Schapira, A. H. V., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb02325.x · Cited by 2,283 · see citing works
The 26S Proteasome: A Molecular Machine Designed for Controlled Proteolysis
Voges, D., Zwickl, P., & Baumeister, W. P. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.1015 · Cited by 1,894 · see citing works
Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria
Turrens, J. F., & Boveris, A. (1980) · Biochemical Journal · doi:10.1042/bj1910421 · Cited by 1,601 · see citing works
The cellular production of hydrogen peroxide
Boveris, A., Oshino, N., & Chance, B. (1972) · Biochemical Journal · doi:10.1042/bj1280617 · Cited by 1,549 · see citing works
Mitochondria, oxygen free radicals, disease and ageing
Raha, S., & Robinson, B. H. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01674-1 · Cited by 1,066 · see citing works
Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
Meng, L., Mohan, R., Kwok, B. H. B., Elofsson, M., Sin, N., & Crews, C. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10403 · Cited by 926 · see citing works
Goldstein, S., Meyerstein, D., & Czapski, G. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90043-t · Cited by 679 · see citing works
Jiang, Z. Y., Woollard, A. C. S., & Wolff, S. P. (1991) · Lipids · doi:10.1007/bf02536169 · Cited by 639 · see citing works
[16] Isolation of subcellular organelles
Storrie, B., & Amadden, E. (1990) · Methods in Enzymology · doi:10.1016/0076-6879(90)82018-w · Cited by 555 · see citing works
Do Mitochondria Produce Oxygen Radicals in vivo?
Nohl, H., & HEGNER, D. (1978) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1978.tb12051.x · Cited by 523 · see citing works
Cubells, J. F., Rayport, S., Rajendran, G., & Sulzer, D. L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-02260.1994 · Cited by 448 · see citing works
Ubiquitin Conjugation Is Not Required for the Degradation of Oxidized Proteins by Proteasome
Shringarpure, R., Grune, T., Mehlhase, J., & Davies, K. J. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206279200 · Cited by 438 · see citing works
Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse.
O'Callaghan, J. P., & Miller, D. B. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22433-8 · Cited by 409 · see citing works
Pitkanen, S., & Robinson, B. H. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118798 · Cited by 388 · see citing works
Inhibition of the uptake of tritiated 5-hydroxytryptamine in brain tissue
Ross, S. B., & Rényi, A. L. (1969) · European Journal of Pharmacology · doi:10.1016/0014-2999(69)90091-0 · Cited by 320 · see citing works
Arai, M., Imai, H., Koumura, T., Yoshida, M., Emoto, K., Umeda, M., Chiba, N., & Nakagawa, Y. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4924 · Cited by 296 · see citing works
Cadet, J. L., Jayanthi, S., & Deng, X. (2003) · The FASEB Journal · doi:10.1096/fj.03-0073rev · Cited by 286 · see citing works
Fumagalli, F., Gainetdinov, R. R., Wang, Y., Valenzano, K. J., Miller, G. W., & Caron, M. G. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02424.1999 · Cited by 241 · see citing works
Deng, X.-L., Wang, Y., Chou, J., & Cadet, J. (2001) · Brain Research. Molecular Brain Research · doi:10.1016/s0169-328x(01)00184-x · Cited by 208 · see citing works
Amphetamines induce apoptosis and regulation of bcl‐x splice variants in neocortical neurons
Stumm, G., Schlegel, J., Schäfer, T., Würz, C., Mennel, H. D., Krieg, J. C., & Vedder, H. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.9.1065 · Cited by 178 · see citing works
Seaton, T. A., Cooper, J. M., & Schapira, A. H. V. (1997) · Brain Research · doi:10.1016/s0006-8993(97)01034-2 · Cited by 177 · see citing works
Gluck, M. R., Moy, L. Y., Jayatilleke, E., Hogan, K. A., Manzino, L., & Sonsalla, P. K. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00549.x · Cited by 152 · see citing works
Arai, M., Imai, H., Sumi, D., Imanaka, T., Takano, T., Chiba, N., & Nakagawa, Y. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1525 · Cited by 129 · see citing works
Deng, X., Cai, N.-S., McCoy, M. T., Chen, W., Trush, M. A., & Cadet, J. L. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00034-5 · Cited by 122 · see citing works
Imam, S. Z., Newport, G. D., Itzhak, Y., Cadet, J. L., Islam, F., Slikker, W., & Ali, S. F. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00029.x · Cited by 113 · see citing works
Preston, K. L., Wagner, G. C., Schuster, C. R., & Seiden, L. S. (1985) · Brain Research · doi:10.1016/0006-8993(85)90153-2 · Cited by 87 · see citing works
Açıkgöz, O., Gönenç, S., Kayatekin, B. M., Uysal, N., Pekçetin, Ç., Şemin, İ., & Güre, A. (1998) · Brain Research · doi:10.1016/s0006-8993(98)01020-8 · Cited by 75 · see citing works
[3H]WIN 35,065–2: A Ligand for Cocaine Receptors in Striatum
Ritz, M. C., Boja, J. W., Grigoriadis, D. E., Zaczek, R. C., Carroll, F. I., Lewis, A. H., & Kuhar, M. J. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb04938.x · Cited by 41 · see citing works
Cocaine Downregulates the Expression of the Mitochondrial Genome in Rat Brain
Dietrich, J., Poirier, R., Aunis, D., & Zwiller, J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1316.042 · Cited by 32 · see citing works
Self-citationZujovic (2000) · doi:10.1002/(sici)1098-1136(20000215)29:4
Flagged first, then by citations
Cited by
Sorted by citations
Oxidative stress in psychiatric disorders: evidence base and therapeutic implications
Ng, F., Berk, M., Dean, O., & Bush, A. I. (2008) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145707008401 · Cited by 1,069 · see citing works
“, 2005), cocaine (Dietrich et al., 2005) and amphetamines (Frey et al.”
BackgroundCasting a Wide Net: Role of Perineuronal Nets in Neural Plasticity
Sorg, B. A., Berretta, S., Blacktop, J. M., Fawcett, J. W., Kitagawa, H., Kwok, J. C. F., & Miquel, M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2351-16.2016 · Cited by 454 · see citing works
“Cocaine produces oxidative stress in neurons (Dietrich et al., 2005; Numa et al., 2008; Sordi et al., 2014; Jang et al., 2015).”
Nuclear Factor κB Signaling Regulates Neuronal Morphology and Cocaine Reward
Russo, S. J., Wilkinson, M. B., Mazei‐Robison, M. S., Dietz, D., Maze, I. S., Krishnan, V., Renthal, W. R., Graham, A., Birnbaum, S. G., Green, T. A., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.6173-08.2009 · Cited by 248 · see citing works
“In contrast to methamphetamine, cocaine, at least at the dosing schedules used here, does not induce cell death or frank injury in the CNS (Dietrich et al., 2005), although it has been shown to alter cell morphology in the NAc and certain other reward-related brain structures (Li et al., 2004;…”
BackgroundCellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs
Cunha‐Oliveira, T., Rego, A. C., & Oliveira, C. R. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.03.002 · Cited by 243 · see citing works
“Cocaine seems to be less toxic than amphetamine, and in most studies apoptotic neuronswere not observed upon exposure to cocaine (Dietrich et al., 2005; Cunha-Oliveira et al., 2006a; Oliveira et al., 2002).”
BackgroundInfluentialNelson, S. K., Bose, S. K., Grunwald, G. K., Myhill, P., & McCord, J. M. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.08.043 · Cited by 215 · see citing works
Glutathione-S-Transferases As Determinants of Cell Survival and Death
Tew, K. D., & Townsend, D. M. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4640 · Cited by 212 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
“However, these changes coincide with increases in levels of glutathione peroxidase and superoxide dismutase, suggesting that compensatory mechanisms may prevent extensive long-term damage (Dietrich et al., 2005; Numa et al., 2008).”
BackgroundChan, S. H. H., Tai, M.-H., Li, C.-Y., & Chan, J. Y. H. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.01.032 · Cited by 149 · see citing works
The role of dopamine receptors in the neurotoxicity of methamphetamine
Ares‐Santos, S., Granado, N., & Moratalla, R. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12049 · Cited by 138 · see citing works
Cunha‐Oliveira, T., Rego, A. C., Cardoso, S. M., Borges, F., Swerdlow, R. H., Macedo, T., & Oliveira, C. R. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.061 · Cited by 126 · see citing works
“In accordance with the present results, Dietrich et al. (2005) recently demonstrated that although cocaine and amphetamine are deleterious to the brain, the adverse consequences of amphetamine exposure are more pronounced.”
BackgroundResultMuriach, M., López‐Pedrajas, R., Barcia, J. M., Sanchez‐Villarejo, M. V., Almansa, I., & Romero, F. J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06794.x · Cited by 122 · see citing works
Decreased brain dopamine cell numbers in human cocaine users
Little, K. Y., Ramssen, E., Welchko, R. M., Volberg, V., Roland, C. J., & Cassin, B. J. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2008.10.034 · Cited by 108 · see citing works
Chandra, R., Engeln, M., Schiefer, C., Patton, M. H., Martin, J. A., Werner, C. T., Riggs, L. M., Francis, T. C., McGlincy, M., Evans, B., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.037 · Cited by 105 · see citing works
“This includes alterations in glucose Neu metabolism, oxidative stress, and cellular respiration, as well as imbalanced glutamate homeostasis (Cunha-Oliveira et al., 2013; Dietrich et al., 2005; Jang et al., 2015; Kalivas, 2009; Pomierny-Chamio1o et al., 2013; Volkow et al., 1991).”
BackgroundCocaine-induced oxidative stress precedes cell death in human neuronal progenitor cells
Poon, H. F., Abdullah, L. I., Mullan, M. A., MULLAN, M. J., & Crawford, F. (2006) · Neurochemistry International · doi:10.1016/j.neuint.2006.06.012 · Cited by 87 · see citing works
Oxidative Stress Biomarkers in Some Rat Brain Structures and Peripheral Organs Underwent Cocaine
Pomierny-Chamioło, L., Moniczewski, A., Wydra, K., Suder, A., & Filip, M. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9335-6 · Cited by 86 · see citing works
“Cocaine intoxication also led to an increase in lipid peroxidation in several brain structures linked to dopamine synthesis and release (Dietrich et al. 2005; Bashkatova et al. 2006).”
BackgroundResultInfluentialTargeting the Progression of Parkinsons Disease
George, J., Mok, S., Moses, D., Wilkins, S., Bush, A., Cherny, R., & Finkelstein, D. (2009) · Current Neuropharmacology · doi:10.2174/157015909787602814 · Cited by 77 · see citing works
A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol
Pereira, R. B., Andrade, P. B., & Valentão, P. (2015) · Neurotoxicity Research · doi:10.1007/s12640-015-9536-x · Cited by 73 · see citing works
Glutathione and redox signaling in substance abuse
Uys, J. D. K., Mulholland, P. J., & Townsend, D. M. (2014) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2014.06.001 · Cited by 73 · see citing works
“In addition, an acute and chronic cocaine injections (20 mg/kg for 10 days) increased ROS, hydrogen peroxide and lipid peroxide generation in the rat frontal cortex and striatum [37].”
BackgroundAssociation of Oxidative Stress with Psychiatric Disorders
Hassan, W., Noreen, H., Gomes, V. D. C., Mohammadzai, I., da Rocha, J. B. T., & Landeira-Fernández, J. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160307145931 · Cited by 73 · see citing works
Psychostimulants and brain dysfunction: A review of the relevant neurotoxic effects
Gonçalves, J., Baptista, S., & Silva, A. P. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.006 · Cited by 71 · see citing works
Involvement of reactive oxygen species in cocaine‐taking behaviors in rats
Jang, E. Y., Ryu, Y., Lee, B. H., Chang, S., Yeo, M. J., Kim, S. H., Folsom, R. J., Schilaty, N. D., Kim, K. J., Yang, C. H., et al. (2015) · Addiction Biology · doi:10.1111/adb.12159 · Cited by 70 · see citing works
“© 2014 Society for the Study of Addiction Addiction Biology, 20, 663–675 including striatum and frontal cortex in rats treated with cocaine (Dietrich et al. 2005; Bashkatova et al. 2006).”
BackgroundAttenuation of Cocaine and Methamphetamine Neurotoxicity by Coenzyme Q10
Klongpanichapak, S., Govitrapong, P., SHARMA, S. K., & Ebadi, M. (2006) · Neurochemical Research · doi:10.1007/s11064-005-9025-3 · Cited by 65 · see citing works
“These observations are consistent with those of other investigators [17, 18].”
Slaker, M. L., Jorgensen, E. T., Hegarty, D. M., Liu, X., Kong, Y., Zhang, F., Linhardt, R. J., Brown, T. E., Aicher, S. A., & Sorg, B. A. (2018) · eneuro · doi:10.1523/eneuro.0221-18.2018 · Cited by 64 · see citing works
“A key mechanism that may link cocaine exposure to changes in PNN and/or PV intensity is cocaine-induced oxidative stress (Dietrich et al., 2005; Jang et al., 2015).”
BackgroundCocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum
López‐Pedrajas, R., Ramírez-Lamelas, D. T., Muriach, B., Sanchez‐Villarejo, M. V., Almansa, I., Vidal‐Gil, L., Romero, F. J., Barcia, J. M., & Muriach, M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00279 · Cited by 63 · see citing works
“Some reports indicate redox status misbalance after cocaine treatment in several brain areas (Dietrich et al., 2005; Muriach et al., 2010; Uys et al., 2011).”
BackgroundOxidative Stress and Drugs of Abuse: An Update
Cunha‐Oliveira, T., Rego, A. C., & Oliveira, C. R. (2013) · Mini-Reviews in Organic Chemistry · doi:10.2174/1570193x113106660026 · Cited by 61 · see citing works
Methamphetamine oxidatively damages parkin and decreases the activity of 26S proteasomein vivo
Moszczyńska, A., & Yamamoto, B. K. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07147.x · Cited by 60 · see citing works
Cocaine-Induced Adaptations in Cellular Redox Balance Contributes to Enduring Behavioral Plasticity
Uys, J. D. K., Knackstedt, L. A., Hurt, P., Tew, K. D., Manevich, Y., Hutchens, S., Townsend, D. M., & Kalivas, P. W. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.143 · Cited by 60 · see citing works
Neurotoxicity of Anhydroecgonine Methyl Ester, a Crack Cocaine Pyrolysis Product
Garcia, R. C. T., Dati, L. M. M., Fukuda, S., Torres, L. H., Moura, S., de Carvalho, N. D., Carrettiero, D. C., Camarini, R., Levada‐Pires, A. C., Yonamine, M., et al. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs140 · Cited by 60 · see citing works
“While dopamine is present in lower concentrations than acetylcholine in the hippocampus, cocaine-induced neurotoxicity in hippocampal cells may be due to toxic dopamine metabolites, which lead to oxidative stress (Dietrich et al., 2005; Poon et al., 2007).”
BackgroundPeripheral toxicity in crack cocaine use disorders
Narvaez, J. C. D. M., Magalhães, P. V. D. S., Fries, G. R., Colpo, G. D., Czepielewski, L. S., Vianna, P., Chies, J. A. B., Rosa, A. R., DIEMEN, L. V., Vieta, E., et al. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.03.045 · Cited by 57 · see citing works
“ocaine induces oxidative damage in cell culture and in the prerontal cortex and striatum of rats [8,37].”
BackgroundDrug-induced neurotoxicity in addiction medicine
Ahmadi‐Soleimani, S. M., Ekhtiari, H., & Cadet, J. L. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.07.004 · Cited by 55 · see citing works
Supraphysiologic-dose anabolic–androgenic steroid use: A risk factor for dementia?
Kaufman, M. J., Kanayama, G., Hudson, J. I., & Pope, H. G. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.02.014 · Cited by 54 · see citing works
Numa, R., Kohen, R., Poltyrev, T., & Yaka, R. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.05.058 · Cited by 55 · see citing works
Walker, J., Winhusen, T. M., STORKSON, J. M., Lewis, D. F., Pariza, M. W., Somoza, E. C., & Somoza, V. (2014) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2430 · Cited by 51 · see citing works
“Cocaine andmethamphetamine increase the level of ROS by different mechanisms (Yamamoto and Zhu, 1998; Dietrich et al., 2005); thus, the response of the body to these two drugs may vary as well.”
BackgroundInfluentialÁlvaro-Bartolomé, M., Harpe, R. L., Callado, L. F., Meana, J. J., & Garcı́a-Sevilla, J. A. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.074 · Cited by 49 · see citing works
Logan, R. W., Parekh, P. K., Kaplan, G. N., Becker-Krail, D. D., Williams, W. P., Yamaguchi, S., Yoshino, J., Shelton, M. A., Zhu, X., Zhang, H., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0061-1 · Cited by 48 · see citing works
Mitoepigenetics and drug addiction
Sadakierska−Chudy, A., Frankowska, M., & Filip, M. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.06.002 · Cited by 46 · see citing works
Dietrich, J., Takemori, H., Dirrig‐Grosch, S., Bertorello, A. M., & Zwiller, J. (2011) · Synapse · doi:10.1002/syn.20988 · Cited by 45 · see citing works
“SDS-PAGE of brain tissue homogenate and immunoblotting were performed as described previously (Dietrich et al., 2005).”
MethodSelf-citationNarayana, P. A., Herrera, J. J., Bockhorst, K. H. J., Esparza‐Coss, E., Xia, Y., Steinberg, J. L., & Moeller, F. G. (2014) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2014.01.005 · Cited by 44 · see citing works
Tannu, N. S., Howell, L. L., & Hemby, S. E. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.53 · Cited by 43 · see citing works
Yasui, Y., & Su, T. (2016) · Journal of Drug and Alcohol Research · doi:10.4303/jdar/235970 · Cited by 42 · see citing works
“Acute and repeated cocaine administration have been described to induce the ROS production in the PFC and striatum in rats, an effect which is usually accompanied by increases of antioxidant enzymatic activities [125].”
BackgroundLax, E., Friedman, A., Croitoru, O., Sudai, E., Ben‐Moshe, H., Redlus, L., Sasson, E., Blumenfeld‐Katzir, T., Assaf, Y., & Yadid, G. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.034 · Cited by 40 · see citing works
Israel, Y., Quintanilla, M. E., Ezquer, F. E., Morales, P., Santapau, D., Berríos‐Cárcamo, P., Ezquer, M., Olivares, B., & Herrera‐Marschitz, M. (2019) · Addiction Biology · doi:10.1111/adb.12853 · Cited by 41 · see citing works
“Brain oxidative stress is generated by most drugs of abuse(14) and seen after a single dose of cocaine.(15) For alcohol, increases in reactive oxygen species follow the oxidation of dopamine released during stimulation of mesolimbic dopamine system,(16-18) while dopamine released is metabolized by monoamine oxidase, g…”
BackgroundHIV Neuropathogenesis in the Presence of a Disrupted Dopamine System
Nickoloff-Bybel, E. A., Calderon, T. M., Gaskill, P. J., & Berman, J. W. (2020) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-020-09927-6 · Cited by 41 · see citing works
“…and Cadet 2009; Kousik et al. 2012), compromising the BBB (Mahajan et al. 2008; Buch et al. 2012; Kousik et al. 2012), increasing oxidative stress (Dietrich et al. 2005; Ferris et al. 2008; Krasnova and Cadet 2009; Melo et al. 2010), and altering dopaminergic neurotransmission (Seiden et al.…”
Shi, X., Yao, D., Gosnell, B. A., & Chen, C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m027656 · Cited by 40 · see citing works
Piper, B. J., Vu, H. L., Safain, M. G., Oliver, A. J., & Meyer, J. S. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.095760 · Cited by 40 · see citing works
Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims
Tannu, N. S., Mash, D. C., & Hemby, S. E. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001914 · Cited by 40 · see citing works
Proteomic analysis of striatal proteins in the rat model of l ‐DOPA‐induced dyskinesia
Valastro, B., Dekundy, A., Krogh, M., Lundblad, M., James, P., Danysz, W., Quack, G., & Cenci, M. A. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04655.x · Cited by 39 · see citing works
NLRP3 Inflammasome Blockade Reduces Cocaine-Induced Microglial Activation and Neuroinflammation
Chivero, E. T., Thangaraj, A., Tripathi, A., Periyasamy, P., Guo, M., & Buch, S. J. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02184-x · Cited by 39 · see citing works
Bu, Q., Yang, Y., Yan, G., Hu, Z., Hu, C., Duan, J.-C., Lv, L., Zhou, J., Zhao, J., Shao, X., et al. (2011) · Journal of Proteomics · doi:10.1016/j.jprot.2011.11.008 · Cited by 36 · see citing works
Cunha‐Oliveira, T., Silva, L. S., Silva, A. M., Moreno, A. J., Oliveira, C. R., & Santos, M. S. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.04.016 · Cited by 37 · see citing works
Foschiera, L. N., Schmitz, F., & Wyse, Â. T. D. S. (2022) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2022.110518 · Cited by 38 · see citing works
Glial-neuronal ensembles: partners in drug addiction-associated synaptic plasticity
Cadet, J. L., & Bisagno, V. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00204 · Cited by 37 · see citing works
“Acute or repeated cocaine administration also generates ROS in dopaminergic rat brain structures (Dietrich et al., 2005).”
BackgroundQuintanilla, M. E., Ezquer, F. E., Morales, P., Santapau, D., Berríos‐Cárcamo, P., Ezquer, M., Herrera‐Marschitz, M., & Israel, Y. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1304-z · Cited by 36 · see citing works
Wildenberg, G. A., Sorokina, A. M., Koranda, J. L., Monical, A., Heer, C., Sheffield, M. E., Zhuang, X., McGehee, D., & Kasthuri, N. (2021) · eLife · doi:10.7554/elife.71981 · Cited by 37 · see citing works
“…that cocaine alters brain energy homeostasis, including changes in oxidative stress, cellular respiration, and enrichments of mitochondrial-related transcripts in NAc brain slice preps ( Dietrich et al., 2005 ; Feng et al., 2014 ; Kalivas, 2009 ; Lehrmann et al., 2003 ; Volkow et al., 1991 ).”
Cocaine Enhances HIV-1–Induced CD4+ T-Cell Apoptosis
Pandhare, J., Addai, A. B., Mantri, C. K., Hager, C., Smith, R. M., Barnett, L., Villalta, F., Kalams, S. A., & Dash, C. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.12.004 · Cited by 35 · see citing works
Cunha‐Oliveira, T., Rego, A. C., Morgadinho, M. T., Macedo, T., & Oliveira, C. R. (2005) · Toxicology · doi:10.1016/j.tox.2005.08.022 · Cited by 35 · see citing works
The ubiquitin-proteasome system and learning-dependent synaptic plasticity – A 10 year update
Patrick, M. B., Omar, N., Werner, C. T., Mitra, S., & Jarome, T. J. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105280 · Cited by 35 · see citing works
Detection of Free and Protein-Bound ortho -Quinones by Near-Infrared Fluorescence
Mazzulli, J. R., Burbulla, L. F., Krainc, D., & Ischiropoulos, H. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04420 · Cited by 34 · see citing works
de Souza, M. F., Gonçales, T. A., Steinmetz, A., Moura, D. J., Saffi, J., Gomez, R., & Barros, H. M. (2014) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12218 · Cited by 32 · see citing works
Cocaine Destroys Gray Matter Brain Cells and Accelerates Brain Aging
Beheshti, I. (2023) · Biology · doi:10.3390/biology12050752 · Cited by 32 · see citing works
“Cocaine increases the production of ROS, which in turn leads to oxidative damage to brain cells [8].”
BackgroundGarcía-Fuster, M. J., Clinton, S. M., Watson, S. J., & Akil, H. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.88 · Cited by 32 · see citing works
“Cunha-Oliveira et al , 2006 ), although the literature concerning cocaine neurotoxicity in adult brain remains inconclusive (”
BackgroundPuglisi‐Allegra, S., Lazzeri, G., Busceti, C. L., Giorgi, F. S., Biagioni, F., & Fornai, F. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105148 · Cited by 31 · see citing works
Sadakierska−Chudy, A., Kotarska, A., Frankowska, M., Jastrzębska, J., Wydra, K., Miszkiel, J., Przegaliński, E., & Filip, M. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0153-3 · Cited by 31 · see citing works
Roles of the ubiquitin proteasome system in the effects of drugs of abuse
Massaly, N., Francès, B., & Moulédous, L. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00099 · Cited by 29 · see citing works
Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats
Gomes, K. M., Inácio, C. G., Valvassori, S. S., Réus, G. Z., Boeck, C. R., Dal-Pizzol, F., & Quevedo, J. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.08.060 · Cited by 34 · see citing works
Soriani, O., & Kourrich, S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01186 · Cited by 29 · see citing works
Targeting redox regulation to treat substance use disorder using N‐acetylcysteine
Womersley, J. S., Townsend, D. M., Kalivas, P. W., & Uys, J. D. K. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14130 · Cited by 29 · see citing works
Liang, J., Nosova, E., Reddon, H., Nolan, S., Socias, M. E., Barrios, R., & Milloy, M. (2020) · AIDS · doi:10.1097/qad.0000000000002551 · Cited by 27 · see citing works
“Other studies on synergistic neurotoxicity of cocaine and HIV-1 membrane proteins support a possible mechanism of crack cocaine mediated HIV disease progression with increased ROS and dysregulation of other cellular signalling pathways [26,28].”
BackgroundThe role of mitochondria in cocaine addiction
Thornton, C., Grad, E., & Yaka, R. (2021) · Biochemical Journal · doi:10.1042/bcj20200615 · Cited by 28 · see citing works
Lipaus, I. F. S., Gomes, E. F., Martins, C. W., Martins-Silva, C., Pires, R. G. W., Malgarin, F., Schuck, P. F., Nakamura-Palacios, E. M., & Rodrigues, L. C. D. M. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.06.020 · Cited by 27 · see citing works
“The antioxidant enzyme SOD catalyses the dismutation of superoxide radicals into the less reactive hydrogen peroxide [52], suggesting that increased activity might be due to an increase in ROS production in this brain region, possibly caused by crack cocaine inhalation.”
Nhu, H., Nguyen, L. T. T., Shin, E., Kim, D.-J., Jeong, J. H., Chung, Y. H., Lei, X. G., Sharma, N., Jang, C., Nabeshima, T., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.12.027 · Cited by 27 · see citing works
da-Rosa, D. D., Valvassori, S. S., Steckert, A. V., Arent, C. O., Ferreira, C. L., Lopes-Borges, J., Varela, R. B., Mariot, E., Dal‐Pizzol, F., Andersen, M. L., et al. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-011-0691-9 · Cited by 26 · see citing works
“Initially, the neurotoxicity of amphetamines was thought to result essentially from reactive oxygen species (ROS) that are formed by the oxidation of dopamine ( Dietrich et al. 2005 ).”
BackgroundTempol attenuates cocaine-induced death of PC12 cells through decreased oxidative damage
Numa, R., Baron, M., Kohen, R., & Yaka, R. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.10.024 · Cited by 26 · see citing works
Wildenberg, G. A., Sorokina, A., Koranda, J. L., Monical, A., Heer, C. M., Sheffield, M. E. J., Zhuang, X., McGehee, D. S., & Kasthuri, B. (2021) · University of Chicago · doi:10.6082/232sj-vk702 · Cited by 27 · see citing works
Effects of Cocaine on Nitric Oxide Production in Bovine Coronary Artery Endothelial Cells
He, J., Yang, S., & Zhang, L. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.087452 · Cited by 24 · see citing works
“In addition, cocaine can increase reactive oxygen species (Moritz et al., 2003; Dietrich et al., 2005) that may contribute to uncoupling of eNOS and a decrease in bioavailable nitric oxide.”
BackgroundCisneros, I. E., Erdenizmenli, M., Cunningham, K. A., Paessler, S., & Dineley, K. T. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.03.019 · Cited by 23 · see citing works
“kB signaling within the NAc, frontal cortex and hippocampus (Dietrich et al., 2005; Jang et al., 2015; Muriach et al., 2010).”
BackgroundChivero, E. T., Sil, S., Singh, S., Thangaraj, A., Gordon, L., Evah-Nzoughe, G., Ferguson, N., Callen, S. E., & Buch, S. J. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-10020-9 · Cited by 24 · see citing works
Role of Mitochondrial Dynamics in Cocaine’s Neurotoxicity
Wen, S., Aki, T., Funakoshi, T., Unuma, K., & Uemura, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105418 · Cited by 24 · see citing works
“Cocaine-triggered apoptotic neuronal death has also been demonstrated in in vivo models in mouse, rat, and human [32,55,56].”
BackgroundA ketogenic diet diminishes behavioral responses to cocaine in young adult male and female rats
Martinez, L. A., Lees, M. E., Ruskin, D. N., & Masino, S. A. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.02.001 · Cited by 22 · see citing works
Zaparte, A., Viola, T. W., Grassi‐Oliveira, R., Morrone, M. D. S., Moreira, J. C. F., & Bauer, M. E. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3779-8 · Cited by 21 · see citing works
S-Glutathionylation and Redox Protein Signaling in Drug Addiction
Womersley, J. S., & Uys, J. D. K. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.10.001 · Cited by 21 · see citing works
Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum
Muñiz, J. A., Gómez, G., González, B., Rivero‐Echeto, M. C., Cadet, J. L., García‐Rill, E., Urbano, F. J., & Bisagno, V. (2016) · Neurotoxicity Research · doi:10.1007/s12640-016-9601-0 · Cited by 21 · see citing works
“It should be noted that chronic cocaine was found to increase reactive oxygen species production in the striatum (Dietrich et al. 2005).”
Macêdo, D. S., Vasconcelos, S. M. M., Andrade‐Neto, M., Belchior, L. D., Júnior, J. E. R. H., Gonçalves, D. O., Fonteles, M. M. D. F., Silva, M. I. G., Aguiar, L. M. V., Viana, G. S. D. B., et al. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.10.001 · Cited by 21 · see citing works
Vicente‐Rodríguez, M., Gramage, E., Herradón, G., & Pérez‐García, C. (2013) · Toxicology · doi:10.1016/j.tox.2013.09.014 · Cited by 20 · see citing works
“In addition, it is interesting to note that a single dose of cocaine within the same dose range has been shown to downregulate mitochondrial genome and to increase the mitochondrial hydrogen peroxide generation together with a reduced functioning of the mitochondrial complex I in the striatum in response to cocaine (D…”
BackgroundResultInfluentialCortical Consequences of HIV-1 Tat Exposure in Rats are Enhanced by Chronic Cocaine
Wayman, W. N., Chen, L., Persons, A. L., & Napier, T. C. (2015) · Current HIV Research · doi:10.2174/0929867322666150311164504 · Cited by 20 · see citing works
“The absence of neuronal death may reflect ROS buffering as cocaine causes a concomitant increase in the production of antioxidant enzymes which prevents the activation of cellular apoptotic signaling cascades [83].”
BackgroundVitcheva, V., Simeonova, R., Kondeva-Burdina, M., & Mitcheva, M. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/157876 · Cited by 19 · see citing works
Cocainomics: New Insights into the Molecular Basis of Cocaine Addiction
Hemby, S. E. (2010) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9189-8 · Cited by 19 · see citing works
“enzyme activity, and elevates reactive oxygen species in dopaminergic projection areas (Dietrich et al. 2005; Macedo et al. 2005).”
BackgroundChange of cystine/glutamate antiporter expression in ethanol-dependent rats
Peana, A. T., Muggironi, G., & Bennardini, F. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00311 · Cited by 18 · see citing works
“Nonetheless, studies in experimental animal models have shown that ethanol (Bailey et al., 1999; Dahchour et al., 2005), cocaine (Dietrich et al., 2005), heroin (Pan et al., 2005), and nicotine (Jain and Jaimes, 2013) increase reactive oxygen species.”
BackgroundCrossroads of Drug Abuse and HIV Infection: Neurotoxicity and CNS Reservoir
Sonti, S., Tyagi, K., Pande, A., Daniel, R., Sharma, A. L., & Tyagi, M. (2022) · Vaccines · doi:10.3390/vaccines10020202 · Cited by 17 · see citing works
Marchese, N. A., Occhieppo, V. B., Basmadjian, O. M., Casarsa, B. S., Baiardi, G., & Bregonzio, C. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14605 · Cited by 17 · see citing works
“The analyses of HPC (Figure 4) indicated that there were no significant differences in the percentage of GFAP nor CD11bpositive area (treatment*drug interaction F(1,23) = 0.00005 p = .99 and F(1,25) = 0.00004 p = .99, respectively).”
BackgroundInfluentialCocaine induces the expression of homer 1b/c, homer 3a/b, and hsp 27 proteins in rat cerebellum
Dietrich, J., Arpin‐Bott, M., Kao, D., Dirrig‐Grosch, S., Aunis, D., & Zwiller, J. (2007) · Synapse · doi:10.1002/syn.20412 · Cited by 16 · see citing works
“We recently reported that acute or repeated cocaine administration to rats generated reactive oxygen species (ROS) in dopaminergic brain structures (Dietrich et al., 2005).”
BackgroundSelf-citationFreese, L., Almeida, F. B., Heidrich, N., Hansen, A. W., Reinhardt, L. S., Steinmetz, A., Moura, D. J., Gomez, R., & Barros, H. M. T. (2018) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2018.04.001 · Cited by 16 · see citing works
“break in the chain of events that ensure genomic stability in dopaminergic brain structures and can induce a potent genotoxic effect, as demonstrated by ROS increase and DNA damage (Pereira et al., 2015; Dietrich et al., 2005; Alvarenga et al., 2010).”
BackgroundInfluentialMöller, M., Fourie, J., & Harvey, B. H. (2018) · Scientific Reports · doi:10.1038/s41598-018-29978-3 · Cited by 16 · see citing works
Role of Multifunctional FADD (Fas-Associated Death Domain) Adaptor in Drug Addiction
Ramos‐Miguel, A., Álvaro-Bartolomé, M., Julià, M., & Jesus, A. (2012) · InTech eBooks · doi:10.5772/34273 · Cited by 15 · see citing works
“However, the aberrant activation of several cell death mechanisms by cocaine, including those mediated by the Fas/FADD complex, in the adult rat brain remains inconclusive (Dietrich et al, 2005; García-Fuster et al., 2009).”
BackgroundPeraile, I., Granado, N., Torres, E., Gutiérrez‐López, M. D., Moratalla, R., Colado, M. I., & O’Shea, E. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3142-5 · Cited by 15 · see citing works
Identification of biochemical and cytotoxic markers in cocaine treated PC12 cells
Badisa, R. B., Batton, C. S., MAZZIO, E. A., Grant, S. C., & Goodman, C. B. (2018) · Scientific Reports · doi:10.1038/s41598-018-21182-7 · Cited by 15 · see citing works
Gomes, E. F., Lipaus, I. F. S., Martins, C. W., Araújo, A. M., Mendonça, J. B., Pelição, F. S., Lebarch, E. C., Rodrigues, L. C. D. M., & Nakamura-Palacios, E. M. (2017) · Neurotoxicity Research · doi:10.1007/s12640-017-9813-y · Cited by 15 · see citing works
“To this end, the integrity of PFC integration with the hippocampus (HPC) and striatum (STR) is essential (Doeller et al. 2005; Floresco et al. 1997; Poch and Campo 2012; Seamans et al. 1998).”
BackgroundNhu, H., Sharma, N., Jeong, J. H., Shin, E., Pham, D. T., Trinh, Q. D., Lee, Y. J., Jang, C., Nah, S.-Y., Bing, G., et al. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.12.017 · Cited by 15 · see citing works
“, superoxide dismutase, glutathione peroxidase, and catalase) (Dietrich et al., 2005; Macedo et al., 2010; Pomierny-Chamiolo et al., 2013).”
InfluentialThe Role of Oxidative Stress in Cocaine Addiction
Beiser, T., & Yaka, R. (2019) · Journal of Neurology and Neuromedicine · doi:10.29245/2572.942x/2019/1.1239 · Cited by 15 · see citing works
Tsai, S.-Y. A., Bendriem, R. M., & Lee, C.-T. D. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.100145 · Cited by 14 · see citing works
“…pathways as revealed by studies in which both acute and chronic cocaine and/or METH exposure generated reactive oxygen species and altered CNS activities in various brain subregions (Bashkatova et al., 2005; Dietrich et al., 2005; Macedo et al., 2005; Pubill et al., 2005; Yamamoto and Zhu, 1998).”
Background
- Authors
- Dietrich, J.-B., Mangeol, A., Revel, M.-O., Burgun, C., Aunis, D., & Zwiller, J.
- Affiliations
- Inserm (FR)
- Corresponding author
- Dietrich, Jean-Bernard
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 48
- Issue
- 7
- Pages
- 965-974
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2061764945
- Cited by
- 168
- References
- 34
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 5 · 2019: 11 · 2018: 13 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 16 · 2013: 11 · 2012: 8
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- cocaine, reactive oxygen species, oxidative stress, antioxidant enzymes, superoxide dismutase, glutathione peroxidase, dopaminergic neurons, frontal cortex, striatum, mitochondrial hydrogen peroxide, mitochondrial complex I, lipid peroxidation, caspase-3, apoptosis, methamphetamine
- MeSH terms
- Animals, Antioxidants, Brain, Cocaine, Dopamine, Enzyme Induction, Glutathione Peroxidase, Male, Superoxide Dismutase, Rats, Wistar, Reactive Oxygen Species, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
