{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:53:45Z","timestamp":1760234025874,"version":"build-2065373602"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-030786","UID\/NEU\/04539\/2019","UID\/NEU\/04539\/2013"],"award-info":[{"award-number":["POCI-01-0145-FEDER-030786","UID\/NEU\/04539\/2019","UID\/NEU\/04539\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"COMPETE_FEDER","award":["POCI-01-0145-FEDER-007440"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007440"]}]},{"name":"Centro 2020 Regional Operational Programmes","award":["CENTRO-01-0145-FEDER-000012: HealthyAging2020","CENTRO-01-0145-FEDER- 000008: BrainHealth 2020"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000012: HealthyAging2020","CENTRO-01-0145-FEDER- 000008: BrainHealth 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>3,4-Methylenedioxypyrovalerone (MDPV), a widely available synthetic cathinone, is a popular substitute for classical controlled drugs of abuse, such as methamphetamine (METH). Although MDPV poses public health risks, its neuropharmacological profile remains poorly explored. This study aimed to provide evidence on that direction. Accordingly, C57BL\/6J mice were exposed to a binge MDPV or METH regimen (four intraperitoneal injections every 2 h, 10 mg\/kg). Locomotor, exploratory, and emotional behavior, in addition to striatal neurotoxicity and glial signature, were assessed within 18\u201324 h, a known time-window encompassing classical amphetamine dopaminergic neurotoxicity. MDPV resulted in unchanged locomotor activity (open field test) and emotional behavior (elevated plus maze, splash test, tail suspension test). Additionally, striatal TH (METH neurotoxicity hallmark), Iba-1 (microglia), GFAP (astrocyte), RAGE, and TLR2\/4\/7 (immune modulators) protein densities remained unchanged after MDPV-exposure. Expectedly, and in sheer contrast with MDPV, METH resulted in decrease general locomotor activity paralleled by a significant striatal TH depletion, astrogliosis, and microglia arborization alterations (Sholl analysis). This comparative study newly highlights that binge MDPV-exposure comes without evident behavioral, neurochemical, and glial changes at a time-point where METH-induced striatal neurotoxicity is clearly evident. Nevertheless, neuropharmacological MDPV signature needs further profiling at different time-points, regimens, and brain regions.<\/jats:p>","DOI":"10.3390\/ph14030271","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T21:42:41Z","timestamp":1615930961000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acute MDPV Binge Paradigm on Mice Emotional Behavior and Glial Signature"],"prefix":"10.3390","volume":"14","author":[{"given":"Mafalda","family":"Campe\u00e3o","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8468-3854","authenticated-orcid":false,"given":"Luciana","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"In\u00eas R.","family":"Pita","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Cristina","family":"Lemos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry I, Medical University Innsbruck, 6020 Innsbruck, Austria"}]},{"given":"Syed F.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arkansas for Medical Sciences (Adjunct Professor), Little Rock, AR 72205, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-3494","authenticated-orcid":false,"given":"F\u00e9lix","family":"Carvalho","sequence":"additional","affiliation":[{"name":"REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, UCIBIO, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7519-1620","authenticated-orcid":false,"given":"Paulo","family":"Rodrigues-Santos","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), Laboratory of Immunology and Oncology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Medicine, Institute of Immunology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9707-4895","authenticated-orcid":false,"given":"Carlos A.","family":"Fontes-Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-7788","authenticated-orcid":false,"given":"Edna","family":"Soares","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]},{"given":"Sofia D.","family":"Viana","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"},{"name":"ESTESC-Coimbra Health School, Pharmacy, Polytechnic Institute of Coimbra, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-3320","authenticated-orcid":false,"given":"Frederico C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"ref_1","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (2020). European Drug Report 2020: Trends and Developments, Publications Office of the European Union."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1080\/10408444.2019.1679087","article-title":"Synthetic cathinones: An evolving class of new psychoactive substances","volume":"49","author":"Goncalves","year":"2019","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.toxlet.2011.10.002","article-title":"3,4-methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online","volume":"208","author":"Coppola","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00204-014-1278-7","article-title":"Raising awareness of new psychoactive substances: Chemical analysis and in vitro toxicity screening of \u2018legal high\u2019 packages containing synthetic cathinones","volume":"89","author":"Araujo","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.pharmthera.2017.10.022","article-title":"Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?","volume":"182","author":"Hondebrink","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.brainresbull.2016.04.011","article-title":"Neurobiology of 3,4-methylenedioxypyrovalerone (MDPV) and alpha-pyrrolidinovalerophenone (alpha-PVP)","volume":"126","author":"Glennon","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2012.11.020","article-title":"Psychoactive \u201cbath salts\u201d: Not so soothing","volume":"698","author":"Baumann","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00204-013-1163-9","article-title":"Khat and synthetic cathinones: A review","volume":"88","author":"Valente","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_9","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (2014). EMCDDA\u2013Europol Joint Report on a New Psychoactive Substance: MDPV (3,4-methylenedioxypyrovalerone), Publications Office of the European Union. Joint Reports."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1476-5381.2012.02145.x","article-title":"Pharmacological characterization of designer cathinones in vitro","volume":"168","author":"Simmler","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/7854_2016_53","article-title":"Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs","volume":"32","author":"Baumann","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.neuro.2012.08.003","article-title":"Effects of synthetic cathinones contained in \u201cbath salts\u201d on motor behavior and a functional observational battery in mice","volume":"33","author":"Marusich","year":"2012","journal-title":"Neurotoxicology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/npp.2016.88","article-title":"Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology","volume":"41","author":"Nguyen","year":"2016","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neuropharm.2013.04.003","article-title":"The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: Self-administration and locomotor activity in rats","volume":"71","author":"Aarde","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/npp.2012.204","article-title":"Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive \u2018bath salts\u2019 products","volume":"38","author":"Baumann","year":"2013","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.drugalcdep.2012.05.011","article-title":"Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats","volume":"126","author":"Huang","year":"2012","journal-title":"Drug Alcohol Depend."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/npp.2012.233","article-title":"In vivo effects of abused \u2018bath salt\u2019 constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: Drug discrimination, thermoregulation, and locomotor activity","volume":"38","author":"Fantegrossi","year":"2013","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1177\/0269881115598415","article-title":"Concentrations of MDPV in rat striatum correlate with the psychostimulant effect","volume":"29","author":"Novellas","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neuropharm.2017.09.004","article-title":"Role of monoaminergic systems and ambient temperature in bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV)-elicited hyperthermia and locomotor stimulation in mice","volume":"134","author":"Gannon","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1177\/0269881118822151","article-title":"Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat","volume":"33","author":"Masniere","year":"2019","journal-title":"J. Psychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1007\/s00213-014-3819-4","article-title":"Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats","volume":"232","author":"Aarde","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1124\/jpet.119.264895","article-title":"3,4-Methylenedioxypyrovalerone: Neuropharmacological Impact of a Designer Stimulant of Abuse on Monoamine Transporters","volume":"374","author":"Magee","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109876","DOI":"10.1016\/j.pnpbp.2020.109876","article-title":"Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference","volume":"100","author":"Puster","year":"2020","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1097\/FBP.0b013e328364166d","article-title":"Locomotor stimulant and discriminative stimulus effects of \u2018bath salt\u2019 cathinones","volume":"24","author":"Gatch","year":"2013","journal-title":"Behav. Pharmacol."},{"key":"ref_25","first-page":"209","article-title":"Neurotoxicology of Synthetic Cathinone Analogs","volume":"32","author":"Anneken","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/jnc.13048","article-title":"3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: Beta-ketoamphetamine modulation of neurotoxicity by the dopamine transporter","volume":"133","author":"Anneken","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ntt.2017.02.003","article-title":"The combined effects of 3,4-methylenedioxymethamphetamine (MDMA) and selected substituted methcathinones on measures of neurotoxicity","volume":"61","author":"Miner","year":"2017","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fnins.2020.00009","article-title":"Hazard Characterization of Synthetic Cathinones Using Viability, Monoamine Reuptake, and Neuronal Activity Assays","volume":"14","author":"Zwartsen","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.neuro.2018.03.007","article-title":"Neurotoxicity screening of new psychoactive substances (NPS): Effects on neuronal activity in rat cortical cultures using microelectrode arrays (MEA)","volume":"66","author":"Zwartsen","year":"2018","journal-title":"Neurotoxicology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Leong, H.S., Philp, M., Simone, M., Witting, P.K., and Fu, S. (2020). Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041370"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.neulet.2016.06.029","article-title":"Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells","volume":"629","author":"Cuevas","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/acschemneuro.6b00421","article-title":"Neurotoxicity of beta-Keto Amphetamines: Deathly Mechanisms Elicited by Methylone and MDPV in Human Dopaminergic SH-SY5Y Cells","volume":"8","author":"Valente","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1007\/s00204-017-1984-z","article-title":"Methylone and MDPV activate autophagy in human dopaminergic SH-SY5Y cells: A new insight into the context of beta-keto amphetamines-related neurotoxicity","volume":"91","author":"Valente","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s12640-018-9924-0","article-title":"Cytotoxic Effects of 3,4-Catechol-PV (One Major MDPV Metabolite) on Human Dopaminergic SH-SY5Y Cells","volume":"35","author":"Coccini","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.104.070961","article-title":"Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation","volume":"311","author":"Thomas","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.1021\/acschemneuro.9b00225","article-title":"Methamphetamine Activates Toll-Like Receptor 4 to Induce Central Immune Signaling within the Ventral Tegmental Area and Contributes to Extracellular Dopamine Increase in the Nucleus Accumbens Shell","volume":"10","author":"Wang","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.toxlet.2020.07.028","article-title":"Methamphetamine induced neuroinflammation in mouse brain and microglial cell line BV2: Roles of the TLR4\/TRIF\/Peli1 signaling axis","volume":"333","author":"Yang","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.molimm.2020.03.013","article-title":"Methamphetamine alters the TLR4 signaling pathway, NF-kappaB activation, and pro-inflammatory cytokine production in LPS-challenged NR-9460 microglia-like cells","volume":"121","author":"Vargas","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111946","DOI":"10.1016\/j.fct.2020.111946","article-title":"Escalating dose-multiple binge methamphetamine treatment elicits neurotoxicity, altering gut microbiota and fecal metabolites in mice","volume":"148","author":"Chen","year":"2021","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/B978-0-12-801284-0.00007-5","article-title":"Neuroimmune basis of methamphetamine toxicity","volume":"118","author":"Loftis","year":"2014","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/s12974-018-1385-0","article-title":"Methamphetamine neurotoxicity, microglia, and neuroinflammation","volume":"15","author":"Shaerzadeh","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neuron.2015.05.019","article-title":"Dealing with Danger in the CNS: The Response of the Immune System to Injury","volume":"87","author":"Gadani","year":"2015","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"603445","DOI":"10.3389\/fphar.2020.603445","article-title":"Toll-Like Receptor 4 Signaling and Drug Addiction","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lwin, T., Yang, J.L., Ngampramuan, S., Viwatpinyo, K., Chancharoen, P., Veschsanit, N., Pinyomahakul, J., Govitrapong, P., and Mukda, S. (2020). Melatonin ameliorates methamphetamine-induced cognitive impairments by inhibiting neuroinflammation via suppression of the TLR4\/MyD88\/NFkappaB signaling pathway in the mouse hippocampus. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 110109.","DOI":"10.1016\/j.pnpbp.2020.110109"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bbamcr.2005.08.006","article-title":"Evaluation of rage isoforms, ligands, and signaling in the brain","volume":"1746","author":"Ding","year":"2005","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1111\/jnc.13682","article-title":"Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson\u2019s disease","volume":"138","author":"Viana","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.ntt.2012.07.005","article-title":"Disruption of striatal glutamatergic\/GABAergic homeostasis following acute methamphetamine in mice","volume":"34","author":"Pereira","year":"2012","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kobeissy, F.H. (2012). Experimental Psychiatric Illness and Drug Abuse Models: From Human to Animal, an Overview. Psychiatric Disorders, Humana Press.","DOI":"10.1007\/978-1-61779-458-2"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/nm0696-699","article-title":"Striatal dopamine nerve terminal markers in human, chronic methamphetamine users","volume":"2","author":"Wilson","year":"1996","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s12640-013-9423-2","article-title":"A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice","volume":"25","author":"Silva","year":"2014","journal-title":"Neurotox. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/s41598-017-01747-8","article-title":"Characterizing microglia activation: A spatial statistics approach to maximize information extraction","volume":"7","author":"Davis","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1007\/s12035-017-0439-0","article-title":"Aquaporin-4 as a New Target against Methamphetamine-Induced Brain Alterations: Focus on the Neurogliovascular Unit and Motivational Behavior","volume":"55","author":"Leitao","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/jcbfm.2015.59","article-title":"The TNF-alpha\/NF-kappaB signaling pathway has a key role in methamphetamine-induced blood-brain barrier dysfunction","volume":"35","author":"Leitao","year":"2015","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ntt.2010.01.006","article-title":"Effect of a neurotoxic dose regimen of (+)-methamphetamine on behavior, plasma corticosterone, and brain monoamines in adult C57BL\/6 mice","volume":"32","author":"Grace","year":"2010","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1007\/s12640-017-9769-y","article-title":"The Cathinones MDPV and alpha-PVP Elicit Different Behavioral and Molecular Effects Following Acute Exposure","volume":"32","author":"Giannotti","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/cns.12649","article-title":"Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice","volume":"23","author":"Fonseca","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8816","DOI":"10.1523\/JNEUROSCI.1067-07.2007","article-title":"Long-term consequences of methamphetamine exposure in young adults are exacerbated in glial cell line-derived neurotrophic factor heterozygous mice","volume":"27","author":"Boger","year":"2007","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000360001","article-title":"Long-term effects of early adolescent methamphetamine exposure on depression-like behavior and the hypothalamic vasopressin system in mice","volume":"36","author":"Joca","year":"2014","journal-title":"Dev. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00213-012-2864-0","article-title":"A dysphoric-like state during early withdrawal from extended access to methamphetamine self-administration in rats","volume":"225","author":"Jang","year":"2013","journal-title":"Psychopharmacology"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gould, T. (2009). Analysis of Grooming Behavior and Its Utility in Studying Animal Stress, Anxiety, and Depression. Mood and Anxiety Related Phenotypes in Mice, Humana Press.","DOI":"10.1007\/978-1-60761-303-9"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1523\/JNEUROSCI.2143-18.2018","article-title":"A Corticotropin Releasing Factor Network in the Extended Amygdala for Anxiety","volume":"39","author":"Pomrenze","year":"2019","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.neuropharm.2018.10.005","article-title":"Neuroadaptive changes and behavioral effects after a sensitization regime of MDPV","volume":"144","author":"Valverde","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.drugalcdep.2017.04.024","article-title":"Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats","volume":"178","author":"Hicks","year":"2017","journal-title":"Drug Alcohol Depend."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0014-2999(03)01272-X","article-title":"The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review","volume":"463","author":"Prut","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.brainres.2005.04.089","article-title":"Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice","volume":"1049","author":"Zhu","year":"2005","journal-title":"Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Krasnova, I.N., Justinova, Z., Ladenheim, B., Jayanthi, S., McCoy, M.T., Barnes, C., Warner, J.E., Goldberg, S.R., and Cadet, J.L. (2010). Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008790"},{"key":"ref_67","first-page":"741","article-title":"Neurotoxicity profiles of substituted amphetamines in the C57BL\/6J mouse","volume":"270","author":"Miller","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s12640-018-9925-z","article-title":"Striatal Reinnervation Process after Acute Methamphetamine-Induced Dopaminergic Degeneration in Mice","volume":"34","author":"Granado","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/jnc.12201","article-title":"Glial reactivity in resistance to methamphetamine-induced neurotoxicity","volume":"125","author":"Friend","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.expneurol.2004.01.010","article-title":"Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity","volume":"187","author":"LaVoie","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuropharm.2018.04.031","article-title":"Functional connectivity, behavioral and dopaminergic alterations 24 h following acute exposure to synthetic bath salt drug methylenedioxypyrovalerone","volume":"137","author":"Pino","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00213-018-5052-z","article-title":"Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine","volume":"236","author":"Aster","year":"2019","journal-title":"Psychopharmacology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1111\/bph.12061","article-title":"Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter","volume":"168","author":"Cameron","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.amjmed.2012.02.019","article-title":"Psychoactive \u201cbath salts\u201d intoxication with methylenedioxypyrovalerone","volume":"125","author":"Ross","year":"2012","journal-title":"Am. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/j.1360-0443.2009.02564.x","article-title":"A review of the clinical pharmacology of methamphetamine","volume":"104","author":"Cruickshank","year":"2009","journal-title":"Addiction"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s00204-020-02949-2","article-title":"In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV)","volume":"95","author":"Araujo","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/npp.2016.121","article-title":"Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse","volume":"42","author":"Lacagnina","year":"2017","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.mehy.2013.06.007","article-title":"Hypothesizing that designer drugs containing cathinones (\u201cbath salts\u201d) have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption","volume":"81","author":"Blum","year":"2013","journal-title":"Med. Hypotheses"},{"key":"ref_79","first-page":"1043","article-title":"RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning\/memory in a mouse model of Alzheimer\u2019s disease","volume":"24","author":"Fang","year":"2010","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/BF00177912","article-title":"The use of a plus-maze to measure anxiety in the mouse","volume":"92","author":"Lister","year":"1987","journal-title":"Psychopharmacology"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Seibenhener, M.L., and Wooten, M.C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp. JoVE.","DOI":"10.3791\/52434-v"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nmeth.3125","article-title":"Neuronal morphometry directly from bitmap images","volume":"11","author":"Ferreira","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1523\/JNEUROSCI.0936-17.2017","article-title":"Abnormal Microglia and Enhanced Inflammation-Related Gene Transcription in Mice with Conditional Deletion of Ctcf in Camk2a-Cre-Expressing Neurons","volume":"38","author":"McGill","year":"2018","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/3\/271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:36:27Z","timestamp":1760160987000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/3\/271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":83,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ph14030271"],"URL":"https:\/\/doi.org\/10.3390\/ph14030271","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2021,3,16]]}}}