{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:43:46Z","timestamp":1775263426734,"version":"3.50.1"},"reference-count":80,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R03 DA026518"],"award-info":[{"award-number":["R03 DA026518"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The freshwater planarian is an emerging animal model in neuroscience due to its centralized nervous system that closely parallels closely parallels the nervous system of vertebrates. Cocaine, an abused drug, is the \u2018founding member\u2019 of the local anesthetic family. Parthenolide, a sesquiterpene lactone, acts as a behavioral and physiological antagonist of cocaine in planarians and rats, respectively. Previous work from our laboratory showed that both parthenolide and cocaine reduced planarian motility and that parthenolide reversed the cocaine-induced motility decrease at concentrations where parthenolide does not affect the movement of the worms. However, the exact mechanism of the cocaine\/parthenolide antagonism is unknown. Here, we report the results of a Schild analysis to explore the parthenolide\/cocaine relationship in the planarian Girardia tigrina. The Schild slopes of a family of concentration\u2013response curves of parthenolide \u00b1 a single concentration of cocaine and vice versa were \u22120.55 and \u22120.36, respectively. These slopes were not statistically different from each other. Interestingly, the slope corresponding to the parthenolide \u00b1 cocaine (but not the cocaine \u00b1 parthenolide) data set was statistically different from \u22121. Our data suggest an allosteric relationship between cocaine and parthenolide for their effect on planarian motility. To the best of our knowledge, this is the first study about the mechanism of action of the antagonism between cocaine and parthenolide. Further studies are needed to determine the specific nature of the parthenolide\/cocaine target(s) in this organism.<\/jats:p>","DOI":"10.3390\/biom14091168","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T09:43:13Z","timestamp":1726652593000},"page":"1168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Schild Analysis of the Interaction between Parthenolide and Cocaine Suggests an Allosteric Relationship for Their Effects on Planarian Motility"],"prefix":"10.3390","volume":"14","author":[{"given":"Jyothi","family":"Kakuturu","sequence":"first","affiliation":[{"name":"Department of Biology, West Chester University, West Chester, PA 19383, USA"},{"name":"MedStar Health, Columbia, MD 21044, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"On\u00e9 R.","family":"Pag\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Biology, West Chester University, West Chester, PA 19383, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.semcdb.2018.04.014","article-title":"Staying in Shape: Planarians as a Model for Understanding Regenerative Morphology","volume":"87","author":"Birkholz","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Reddien, P.W. (2021). Positional Information and Stem Cells Combine to Result in Planarian Regeneration. Cold Spring Harb. Perspect. Biol., 14.","DOI":"10.1101\/cshperspect.a040717"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"dev167684","DOI":"10.1242\/dev.167684","article-title":"Model Systems for Regeneration: Planarians","volume":"146","author":"Ivankovic","year":"2019","journal-title":"Development"},{"key":"ref_4","unstructured":"Pag\u00e1n, O.R. (2014). The First Brain: The Neuroscience of Planarians, Oxford University Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13276","DOI":"10.1111\/cpr.13276","article-title":"An Insight into Planarian Regeneration","volume":"55","author":"Ge","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/dvg.22872","article-title":"SmedGD 2.0: The Schmidtea mediterranea Genome Database","volume":"53","author":"Robb","year":"2015","journal-title":"Genesis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"D764","DOI":"10.1093\/nar\/gkv1148","article-title":"PlanMine\u2014A Mineable Resource of Planarian Biology and Biodiversity","volume":"44","author":"Brandl","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00427-007-0188-6","article-title":"Regenerating the Central Nervous System: How Easy for Planarians!","volume":"217","year":"2007","journal-title":"Dev. Genes. Evol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1242\/dmm.006692","article-title":"The Planarian Flatworm: An in Vivo Model for Stem Cell Biology and Nervous System Regeneration","volume":"4","author":"Gentile","year":"2011","journal-title":"Dis. Models Mech."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/reg2.56","article-title":"Go Ahead, Grow a Head! A Planarian\u2019s Guide to Anterior Regeneration: Planarian Anterior Regeneration","volume":"3","author":"Owlarn","year":"2016","journal-title":"Regeneration"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ross, K.G., Currie, K.W., Pearson, B.J., and Zayas, R.M. (2017). Nervous System Development and Regeneration in Freshwater Planarians. WIREs Dev. Biol., 6.","DOI":"10.1002\/wdev.266"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101960","DOI":"10.1016\/j.gde.2022.101960","article-title":"Cellular Diversity and Developmental Hierarchy in the Planarian Nervous System","volume":"76","author":"Wyss","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1053\/spen.2002.32502","article-title":"When Does a Ganglion Become a Brain? Evolutionary Origin of the Central Nervous System","volume":"9","author":"Sarnat","year":"2002","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1017\/S031716710003537X","article-title":"The Brain of the Planarian as the Ancestor of the Human Brain","volume":"12","author":"Sarnat","year":"1985","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cbpc.2008.01.009","article-title":"Neuropharmacology and Behavior in Planarians: Translations to Mammals","volume":"147","author":"Buttarelli","year":"2008","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1017\/S0031182005008565","article-title":"Classical Transmitters and Their Receptors in Flatworms","volume":"131","author":"Ribeiro","year":"2006","journal-title":"Parasitology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0925-4773(02)00134-X","article-title":"The Expression of Neural-Specific Genes Reveals the Structural and Molecular Complexity of the Planarian Central Nervous System","volume":"116","author":"Kudome","year":"2002","journal-title":"Mech. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.drugalcdep.2011.04.001","article-title":"Nicotine Behavioral Pharmacology: Clues from Planarians","volume":"118","author":"Rawls","year":"2011","journal-title":"Drug Alcohol. Depend."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.neulet.2016.09.005","article-title":"Cotinine Antagonizes the Behavioral Effects of Nicotine Exposure in the Planarian Girardia tigrina","volume":"632","author":"Bach","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.pbb.2013.09.012","article-title":"Opioid Receptor Types Involved in the Development of Nicotine Physical Dependence in an Invertebrate (Planaria) Model","volume":"112","author":"Raffa","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.neuroscience.2013.05.010","article-title":"Planarians Require an Intact Brain to Behaviorally React to Cocaine, but Not to React to Nicotine","volume":"246","author":"Deats","year":"2013","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sal, F., Prados, J., and Urcelay, G.P. (2021). Nicotine Chronic Tolerance Development and Withdrawal in the Planaria (Schmidtea mediterranea). Pharmacol. Biochem. Behav., 200.","DOI":"10.1016\/j.pbb.2020.173075"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1007\/s11064-015-1512-6","article-title":"Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians","volume":"40","author":"Montgomery","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejphar.2009.05.022","article-title":"A Cembranoid from Tobacco Prevents the Expression of Nicotine-Induced Withdrawal Behavior in Planarian Worms","volume":"615","author":"Rowlands","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.neuropharm.2014.01.002","article-title":"Levamisole and Cocaine Synergism: A Prevalent Adulterant Enhances Cocaine\u2019s Action in Vivo","volume":"79","author":"Tallarida","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.alcohol.2014.07.006","article-title":"Ethanol and Cocaine: Environmental Place Conditioning, Stereotypy, and Synergism in Planarians","volume":"48","author":"Tallarida","year":"2014","journal-title":"Alcohol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.brainres.2004.10.052","article-title":"Description and Quantification of Cocaine Withdrawal Signs in Planaria","volume":"1032","author":"Raffa","year":"2005","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1387\/ijdb.160328op","article-title":"Planaria: An Animal Model That Integrates Development, Regeneration and Pharmacology","volume":"61","year":"2017","journal-title":"Int. J. Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tsuchiya, H. (2017). Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity. Molecules, 22.","DOI":"10.3390\/molecules22081369"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2174\/1568026013395335","article-title":"From Cocaine to Ropivacaine: The History of Local Anesthetic Drugs","volume":"1","author":"Ruetsch","year":"2001","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"K\u00f6rner, J., Albani, S., Sudha Bhagavath Eswaran, V., Roehl, A.B., Rossetti, G., and Lampert, A. (2022). Sodium Channels and Local Anesthetics\u2014Old Friends with New Perspectives. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.837088"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nepal, B., Das, S., Reith, M.E., and Kortagere, S. (2023). Overview of the Structure and Function of the Dopamine Transporter and Its Protein Interactions. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1150355"},{"key":"ref_33","first-page":"814","article-title":"Recent Advances on the Structural Modification of Parthenolide and Its Derivatives as Anticancer Agents","volume":"20","author":"Liu","year":"2022","journal-title":"Chin. J. Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1007\/s10753-011-9346-0","article-title":"Parthenolide, a Sesquiterpene Lactone, Expresses Multiple Anti-Cancer and Anti-Inflammatory Activities","volume":"35","author":"Mathema","year":"2012","journal-title":"Inflammation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1039\/C9NP00049F","article-title":"Advances in Chemistry and Bioactivity of Parthenolide","volume":"37","author":"Freund","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e17843","DOI":"10.1016\/j.heliyon.2023.e17843","article-title":"Trends in Parthenolide Research over the Past Two Decades: A Bibliometric Analysis","volume":"9","author":"Liu","year":"2023","journal-title":"Heliyon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/cod.14419","article-title":"The Sesquiterpene Lactone Mix: A Review of Past, Present and Future Aspects","volume":"89","author":"Paulsen","year":"2023","journal-title":"Contact Dermat."},{"key":"ref_38","unstructured":"Pag\u00e1n, O.R. (2005). Synthetic Local Anesthetics as Alleviators of Cocaine Inhibition of the Human Dopamine Transporter. [Ph.D. Dissertation, Cornell University]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.pbb.2007.12.008","article-title":"Reversal of Cocaine-Induced Planarian Behavior by Parthenolide and Related Sesquiterpene Lactones","volume":"89","author":"Rowlands","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ejphar.2008.01.012","article-title":"Parthenolide Prevents the Expression of Cocaine-Induced Withdrawal Behavior in Planarians","volume":"583","author":"Rowlands","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.pbb.2011.08.013","article-title":"Minimal Structural Requirements of Alkyl \u03b3-Lactones Capable of Antagonizing the Cocaine-Induced Motility Decrease in Planarians","volume":"100","author":"Baker","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1387\/ijdb.113486op","article-title":"Planarians in Pharmacology: Parthenolide Is a Specific Behavioral Antagonist of Cocaine in the Planarian Girardia tigrina","volume":"56","author":"Baker","year":"2012","journal-title":"Int. J. Dev. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2174\/157015911795017010","article-title":"Parthenolide Blocks Cocaine\u2019s Effect on Spontaneous Firing Activity of Dopaminergic Neurons in the Ventral Tegmental Area","volume":"9","author":"Schwarz","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neulet.2006.08.073","article-title":"Toxicity and Behavioral Effects of Dimethylsulfoxide in Planaria","volume":"407","author":"Rowlands","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S1056-8719(01)00152-6","article-title":"Quantitative Assessment of Dopamine D2 Antagonist Activity Using Invertebrate (Planaria) Locomotion as a Functional Endpoint","volume":"45","author":"Raffa","year":"2001","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_46","first-page":"A48","article-title":"The Flatworm Planaria as a Toxicology and Behavioral Pharmacology Animal Model in Undergraduate Research Experiences","volume":"7","author":"Coudron","year":"2009","journal-title":"J. Undergrad. Neurosci. Educ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1096\/fasebj.11.11.9285481","article-title":"The Hill Equation Revisited: Uses and Misuses","volume":"11","author":"Weiss","year":"1997","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1134\/S0006350922020142","article-title":"New Interpretation of the Hill Coefficient","volume":"67","author":"Lavrinenko","year":"2022","journal-title":"Biophysics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00407-012-0098-5","article-title":"The Hill Equation and the Origin of Quantitative Pharmacology","volume":"66","author":"Gesztelyi","year":"2012","journal-title":"Arch. Hist. Exact. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1472-8206.2008.00633.x","article-title":"The Hill Equation: A Review of Its Capabilities in Pharmacological Modelling","volume":"22","author":"Goutelle","year":"2008","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1139\/y82-036","article-title":"The Schild Regression in the Process of Receptor Classification","volume":"60","author":"Kenakin","year":"1982","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tallarida, R.J. (2000). Drug Synergism and Dose-Effect Data Analysis, Chapman & Hall\/CRC.","DOI":"10.1201\/9781420036107"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.pharmthera.2006.08.002","article-title":"Interactions between Drugs and Occupied Receptors","volume":"113","author":"Tallarida","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.tips.2007.09.011","article-title":"Why the Schild Method Is Better than Schild Realised","volume":"28","author":"Colquhoun","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1093\/bioinformatics\/btz802","article-title":"PlanExp: Intuitive Integration of Complex RNA-Seq Datasets with Planarian Omics Resources","volume":"36","author":"Abril","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40851-018-0102-2","article-title":"Draft Genome of Dugesia japonica Provides Insights into Conserved Regulatory Elements of the Brain Restriction Gene Nou-Darake in Planarians","volume":"4","author":"An","year":"2018","journal-title":"Zool. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00044-023-03181-0","article-title":"Bioactivities and the Structural Modification of Parthenolide: A Review","volume":"33","author":"Wu","year":"2024","journal-title":"Med. Chem. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhu, S., Sun, P., Bennett, S., Charlesworth, O., Tan, R., Peng, X., Gu, Q., Kujan, O., and Xu, J. (2023). The Therapeutic Effect and Mechanism of Parthenolide in Skeletal Disease, Cancers, and Cytokine Storm. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1111218"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1385\/CT:3:2:141","article-title":"Cocaine, Not Morphine, Causes the Generation of Reactive Oxygen Species and Activation of NF-\u03baB in Transiently Cotransfected Heart Cells","volume":"3","author":"Hargrave","year":"2003","journal-title":"Cardiovasc. Toxicol"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1093\/ijnp\/pyy031","article-title":"Transcriptome Sequencing Reveals Candidate NF-\u03baB Target Genes Involved in Repeated Cocaine Administration","volume":"21","author":"Wang","year":"2018","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Pedrajas, R., Almansa, I., S\u00e1nchez-Villarejo, M.V., Muriach, B., Barcia, J.M., Romero, F.J., and Muriach, M. (2021). Role of Hippocampal NF-\u03baB and GluN2B in the Memory Acquisition Impairment of Experiences Gathered Prior to Cocaine Administration in Rats. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-99448-w"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.bbi.2022.03.002","article-title":"Nuclear Factor Kappa B Signaling within the Rat Nucleus Accumbens Core Sex-Dependently Regulates Cue-Induced Cocaine Seeking and Matrix Metalloproteinase-9 Expression","volume":"102","author":"Namba","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1523\/JNEUROSCI.6173-08.2009","article-title":"Nuclear Factor \u03baB Signaling Regulates Neuronal Morphology and Cocaine Reward","volume":"29","author":"Russo","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/FBP.0000000000000236","article-title":"Benzodiazepine Inhibits Anxiogenic-like Response in Cocaine or Ethanol Withdrawn Planarians","volume":"27","author":"Nayak","year":"2016","journal-title":"Behav. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jneumeth.2017.10.010","article-title":"PLDT (Planarian Light\/Dark Test): An Invertebrate Assay to Quantify Defensive Responding and Study Anxiety-like Effects","volume":"293","author":"Zewde","year":"2018","journal-title":"J. Neurosci. Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/FBP.0b013e32833b0098","article-title":"First Evidence That Drugs of Abuse Produce Behavioral Sensitization and Cross Sensitization in Planarians","volume":"21","author":"Rawls","year":"2010","journal-title":"Behav. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neulet.2015.03.021","article-title":"Persistent Conditioned Place Preference to Cocaine and Withdrawal Hypo-Locomotion to Mephedrone in the Flatworm Planaria","volume":"593","author":"Hutchinson","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.cub.2020.11.055","article-title":"Parthenolide Destabilizes Microtubules by Covalently Modifying Tubulin","volume":"31","author":"Hotta","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cbi.2004.07.005","article-title":"Microtubule-Interfering Activity of Parthenolide","volume":"149","author":"Miglietta","year":"2004","journal-title":"Chem. -Biol. Interact."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cbi.2003.10.008","article-title":"A Sesquiterpene Lactone, Costunolide, Interacts with Microtubule Protein and Inhibits the Growth of MCF-7 Cells","volume":"147","author":"Bocca","year":"2004","journal-title":"Chem. -Biol. Interact."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"R83","DOI":"10.1186\/bcr3477","article-title":"Parthenolide and Costunolide Reduce Microtentacles and Tumor Cell Attachment by Selectively Targeting Detyrosinated Tubulin Independent from NF-\u03baB Inhibition","volume":"15","author":"Whipple","year":"2013","journal-title":"Breast Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1007\/s11033-021-06336-7","article-title":"Effect of Ethanol and Cocaine on [11C]MPC-6827 Uptake in SH-SY5Y Cells","volume":"48","author":"Damuka","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.1523\/JNEUROSCI.0024-19.2019","article-title":"Synaptic Microtubule-Associated Protein EB3 and SRC Phosphorylation Mediate Structural and Behavioral Adaptations During Withdrawal from Cocaine Self-Administration","volume":"39","author":"Calipari","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Damuka, N., Martin, T.J., Bansode, A.H., Krizan, I., Martin, C.W., Miller, M., Whitlow, C.T., Nader, M.A., and Solingapuram Sai, K.K. (2022). Initial Evaluations of the Microtubule-Based PET Radiotracer, [11C]MPC-6827 in a Rodent Model of Cocaine Abuse. Front. Med., 9.","DOI":"10.3389\/fmed.2022.817274"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"RP88279","DOI":"10.7554\/eLife.88279.3","article-title":"Inhibition of Microtubule Detyrosination by Parthenolide Facilitates Functional CNS Axon Regeneration","volume":"12","author":"Leibinger","year":"2023","journal-title":"eLife"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Rabiasz, A., and Zi\u0119tkiewicz, E. (2023). Schmidtea mediterranea as a Model Organism to Study the Molecular Background of Human Motile Ciliopathies. IJMS, 24.","DOI":"10.3390\/ijms24054472"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0091-679X(08)93004-1","article-title":"Schmidtea mediterranea","volume":"Volume 93","author":"Rompolas","year":"2009","journal-title":"Methods in Cell Biology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1387\/ijdb.180145op","article-title":"Measuring Functional Brain Recovery in Regenerating Planarians by Assessing the Behavioral Response to the Cholinergic Compound Cytisine","volume":"64","author":"Baker","year":"2020","journal-title":"Int. J. Dev. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2174\/138955706777934937","article-title":"Naturally Occurring NF-kappaB Inhibitors","volume":"6","author":"Nam","year":"2006","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1271\/bbb.120619","article-title":"Santonin-Related Compound 2 Inhibits the Nuclear Translocation of NF-\u03baB Subunit P65 by Targeting Cysteine 38 in TNF-\u03b1-Induced NF-\u03baB Signaling Pathway","volume":"76","author":"Tamura","year":"2012","journal-title":"Biosci. Biotechnol. Biochem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/9\/1168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:58:29Z","timestamp":1760111909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/9\/1168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":80,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["biom14091168"],"URL":"https:\/\/doi.org\/10.3390\/biom14091168","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.01.02.474598","asserted-by":"object"}]},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,18]]}}}