{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:23:06Z","timestamp":1787026986789,"version":"build-2736575974"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Several new synthetic cathinones, which mimic the effect of classical psychostimulants such as cocaine or MDMA, have appeared in the global illicit drug market in the last decades. In fact, the illicit drug market is continually evolving by constantly adding small modifications to the common chemical structure of synthetic cathinones. Thus, the aim of this study was to investigate the\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    structure\u2013activity relationship (SAR) of six novel synthetic cathinones currently popular as recreational drugs, pentedrone, pentylone, N-ethyl-pentedrone (NEPD), N-ethyl-pentylone (NEP), 4-methyl-pentedrone (4-MPD), and 4-methyl-ethylaminopentedrone (4-MeAP), which structurally differ in the absence or presence of different aromatic substituents and in their amino terminal group. Human embryonic kidney (HEK293) cells expressing the human isoforms of SERT and DAT were used for the uptake inhibition and release assays. Moreover, Swiss CD-1 mice were used to investigate the psychostimulant effect, rewarding properties (3, 10, and 30\u00a0mg\/kg, i.p.), and the induction of immediate-early genes (IEGs), such as\n                    <jats:italic>Arc<\/jats:italic>\n                    and\n                    <jats:italic>c-fos<\/jats:italic>\n                    in the dorsal striatum (DS) and ventral striatum (VS) as well as\n                    <jats:italic>bdnf<\/jats:italic>\n                    in the medial prefrontal cortex (mPFC), of the test compounds. Our results demonstrated that all tested synthetic cathinones are potent dopamine (DA) uptake inhibitors, especially the N-ethyl analogs, while the ring-substituted cathinones tested showed higher potency as SERT inhibitors than their no ring-substituted analogs. Moreover, unlike NEP, the remaining test compounds showed clear \u201chybrid\u201d properties, acting as DAT blockers but SERT substrates. Regarding the locomotion, NEP and NEPD were more efficacious (10\u00a0mg\/kg) than their N-methyl analogs, which correlates with their higher potency inhibiting the DAT and an overexpression of\n                    <jats:italic>Arc<\/jats:italic>\n                    levels in the DS and VS. Furthermore, all compounds tested induced an increase in\n                    <jats:italic>c-fos<\/jats:italic>\n                    expression in the DS, except for 4-MPD, the least effective compound in inducing hyperlocomotion. Moreover, NEP induced an up-regulation of\n                    <jats:italic>bdnf<\/jats:italic>\n                    in the mPFC that correlates with its 5-HTergic properties. Finally, the present study demonstrated for the first time that NEP, 4-MPD, and 4-MeAP induce reward in mice. Altogether, this study provides valuable information about the mechanism of action and psychostimulant and rewarding properties as well as changes in the expression of IEGs related to addiction induced by novel second-generation synthetic cathinones.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2021.749429","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T01:16:30Z","timestamp":1635210990000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":43,"title":["Structure\u2013Activity Relationship of Novel Second-Generation Synthetic Cathinones: Mechanism of Action, Locomotion, Reward, and Immediate-Early Genes"],"prefix":"10.3389","volume":"12","author":[{"given":"Nuria","family":"Nadal-Gratac\u00f3s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Sofia","family":"Alberto-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00edriam","family":"Rodr\u00edguez-Soler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edurne","family":"Urquizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Espinosa-Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"J\u00e4ntsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Holy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Batllori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Berzosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pubill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Camarasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald H.","family":"Sitte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Escubedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"L\u00f3pez-Arnau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/39885","article-title":"Anterograde Transport of Brain-Derived Neurotrophic Factor and its Role in the Brain","volume":"389","author":"Altar","year":"1997","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"626906","DOI":"10.3389\/fnbeh.2021.626906","article-title":"Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do We Have a Translational Perspective?","volume":"15","author":"Arosio","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1460-9568.2008.06601.x","article-title":"Differential Regulation of Psychostimulant-Induced Gene Expression of Brain Derived Neurotrophic Factor and the Immediate-Early Gene Arc in the Juvenile and Adult Brain","volume":"29","author":"Banerjee","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/164_2018_178","article-title":"Neuropharmacology of Synthetic Cathinones","volume":"252","author":"Baumann","year":"2018","journal-title":"Handb. Exp. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s11419-019-00486-x","article-title":"Case Report on Two-Cathinones Abuse: MPHP and N-Ethyl-4\u2032methylnorpentedrone, with a Fatal Outcome","volume":"38","author":"Benedicte","year":"2020","journal-title":"Forensic Toxicol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1111\/bph.13030","article-title":"Quantitative Structure-Activity Relationship Analysis of the Pharmacology of Para-Substituted Methcathinone Analogues","volume":"172","author":"Bonano","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"110659","DOI":"10.1016\/j.forsciint.2020.110659","article-title":"Fatal Intoxication Involving 4-methylpentedrone (4-MPD) in a Context of Chemsex","volume":"319","author":"Cartiser","year":"2021","journal-title":"Forensic Sci. Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.cell.2021.01.034","article-title":"Antidepressant Drugs Act by Directly Binding to TRKB Neurotrophin Receptors","volume":"184","author":"Casarotto","year":"2021","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1523\/JNEUROSCI.17-07-02295.1997","article-title":"Distribution of Brain-Derived Neurotrophic Factor (BDNF) Protein and mRNA in the normal Adult Rat CNS: Evidence for Anterograde Axonal Transport","volume":"17","author":"Conner","year":"1997","journal-title":"J. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.toxlet.2012.03.009","article-title":"Synthetic Cathinones: Chemistry, Pharmacology and Toxicology of a New Class of Designer Drugs of Abuse Marketed as \"bath Salts\" or \"plant Food\"","volume":"211","author":"Coppola","year":"2012","journal-title":"Toxicol. Lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/dta.2502","article-title":"Analytical Quantification, Intoxication Case Series, and Pharmacological Mechanism of Action for N-Ethylnorpentylone (N-Ethylpentylone or Ephylone)","volume":"11","author":"Costa","year":"2019","journal-title":"Drug Test. Anal."},{"key":"B13","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/s0014-2999(99)00538-5","article-title":"Inhibition of Plasma Membrane Monoamine Transporters by Beta-Ketoamphetamines","volume":"381","author":"Cozzi","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"B14","unstructured":"Emerging Threat Report2018"},{"key":"B15","unstructured":"National Forensic Laboratory Information System: 2016 Annual Report2016"},{"key":"B16","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.neuropharm.2018.01.020","article-title":"\"Ecstasy\" to Addiction: Mechanisms and Reinforcing Effects of Three Synthetic Cathinone Analogs of MDMA","volume":"133","author":"Dolan","year":"2018","journal-title":"Neuropharmacology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/J.BCP.2019.02.004","article-title":"7,8-Dihydroxyflavone Blocks the Development of Behavioral Sensitization to MDPV, but Not to Cocaine: Differential Role of the BDNF-TrkB Pathway","volume":"163","author":"Duart-Castells","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"108475","DOI":"10.1016\/j.neuropharm.2021.108475","article-title":"Role of Amino Terminal Substitutions in the Pharmacological, Rewarding and Psychostimulant Profiles of Novel Synthetic Cathinones","volume":"186","author":"Duart-Castells","year":"2021","journal-title":"Neuropharmacology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1007\/s00213-018-5059-5","article-title":"Structure-activity Relationships of bath Salt Components: Substituted Cathinones and Benzofurans at Biogenic Amine Transporters","volume":"236","author":"Eshleman","year":"2019","journal-title":"Psychopharmacology (Berl)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1046\/j.1471-4159.1995.64052377.x","article-title":"Activation of Arc, a Putative \"effector\" Immediate Early Gene, by Cocaine in Rat Brain","volume":"64","author":"Fosnaugh","year":"1995","journal-title":"J. Neurochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1002\/ams2.182","article-title":"Clinical and Toxicological Findings of Acute Intoxication with Synthetic Cannabinoids and Cathinones","volume":"3","author":"Fujita","year":"2015","journal-title":"Acute Med. Surg."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1124\/mol.106.026302","article-title":"Corticostriatal Up-Regulation of Activity-Regulated Cytoskeletal-Associated Protein Expression after Repeated Exposure to Cocaine","volume":"70","author":"Fumagalli","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3389\/fnbeh.2018.00079","article-title":"Immediate Early Genes, Memory and Psychiatric Disorders: Focus on C-Fos, Egr1 and Arc","volume":"12","author":"Gallo","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.drugalcdep.2019.02.016","article-title":"Locomotor Activity and Discriminative Stimulus Effects of Five Novel Synthetic Cathinone Analogs in Mice and Rats","volume":"199","author":"Gatch","year":"2019","journal-title":"Drug Alcohol Depend"},{"key":"B25","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1097\/FBP.0000000000000540","article-title":"Methylenedioxymethamphetamine-like Discriminative Stimulus Effects of Seven Cathinones in Rats","volume":"31","author":"Gatch","year":"2020","journal-title":"Behav. Pharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1007\/s00213-014-3755-3","article-title":"Discriminative and Locomotor Effects of Five Synthetic Cathinones in Rats and Mice","volume":"232","author":"Gatch","year":"2015","journal-title":"Psychopharmacology (Berl)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/J.NEUBIOREV.2009.11.009","article-title":"Role of BDNF and GDNF in Drug Reward and Relapse: A Review","volume":"35","author":"Ghitza","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkaa194","article-title":"Method Validation of Seven Synthetic Cathinones by LC-MS-MS Analysis and the Prevalence of N-Ethylpentylone in Postmortem Casework","author":"Giachetti","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1007\/s12640-017-9769-y","article-title":"The Cathinones MDPV and \u03b1-PVP Elicit Different Behavioral and Molecular Effects Following Acute Exposure","volume":"32","author":"Giannotti","year":"2017","journal-title":"Neurotox. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1021\/acschemneuro.0c00797","article-title":"Eutylone and its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation","volume":"12","author":"Glatfelter","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/7854_2016_41","article-title":"Structure-Activity Relationships of Synthetic Cathinones","volume":"32","author":"Glennon","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1080\/10408444.2019.1679087","article-title":"Synthetic Cathinones: an Evolving Class of New Psychoactive Substances","volume":"49","author":"Gon\u00e7alves","year":"2019","journal-title":"Crit. Rev. Toxicol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.taap.2017.05.010","article-title":"Impact of Common Clandestine Structural Modifications on Synthetic Cathinone \"bath Salt\" Pharmacokinetics","volume":"328","author":"Grecco","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.neubiorev.2014.03.012","article-title":"The Serotonin-BDNF Duo: Developmental Implications for the Vulnerability to Psychopathology","volume":"43","author":"Homberg","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/adb.12299","article-title":"The New Stimulant Designer Compound Pentedrone Exhibits Rewarding Properties and Affects Dopaminergic Activity","volume":"22","author":"Hwang","year":"2017","journal-title":"Addict. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.neuropharm.2017.09.002","article-title":"Locomotor and Reinforcing Effects of Pentedrone, Pentylone and Methylone in Rats","volume":"134","author":"Javadi-Paydar","year":"2018","journal-title":"Neuropharmacology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1021\/cn4001236","article-title":"\"Deconstruction\" of the Abused Synthetic Cathinone Methylenedioxypyrovalerone (MDPV) and an Examination of Effects at the Human Dopamine Transporter","volume":"4","author":"Kolanos","year":"2013","journal-title":"ACS Chem. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/j.1365-2826.2008.01734.x","article-title":"Measurement of Immediate-Early Gene Activation- C-Fos and beyond","volume":"20","author":"Kov\u00e1cs","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/jat\/bky025","article-title":"N-ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens","volume":"42","author":"Krotulski","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1006\/nlme.1998.3836","article-title":"Immediate-early Genes and Synaptic Function","volume":"70","author":"Lanahan","year":"1998","journal-title":"Neurobiol. Learn. Mem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1093\/jat\/bkaa071","article-title":"Determination of 30 Synthetic Cathinones in Postmortem Blood Using LC-MS-MS","volume":"44","author":"Lau","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1097\/00001756-200502080-00022","article-title":"A Single Cocaine Exposure Increases BDNF and D3 Receptor Expression: Implications for Drug-Conditioning","volume":"16","author":"Le Foll","year":"2005","journal-title":"Neuroreport"},{"key":"B43","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1097\/FBP.0000000000000484","article-title":"Effects of N-Ethylpentylone on Locomotor Activity and Anxiety-like Behavior in Rats","volume":"30","author":"Li","year":"2019","journal-title":"Behav. Pharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.bbr.2014.11.018","article-title":"Multiple Faces of BDNF in Cocaine Addiction","volume":"279","author":"Li","year":"2015","journal-title":"Behav. Brain Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1111\/bph.13771","article-title":"Exposure of Adolescent Mice to 3,4-methylenedioxypyrovalerone Increases the Psychostimulant, Rewarding and Reinforcing Effects of Cocaine in Adulthood","volume":"174","author":"L\u00f3pez-Arnau","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/j.1476-5381.2012.01998.x","article-title":"Comparative Neuropharmacology of Three Psychostimulant Cathinone Derivatives: Butylone, Mephedrone and Methylone","volume":"167","author":"L\u00f3pez-Arnau","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s11419-017-0385-6","article-title":"The Newest Cathinone Derivatives as Designer Drugs: an Analytical and Toxicological Review","volume":"36","author":"Majchrzak","year":"2018","journal-title":"Forensic Toxicol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/sj.npp.1301571","article-title":"Interaction between BDNF and Serotonin: Role in Mood Disorders","volume":"33","author":"Martinowich","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.neuropharm.2014.02.016","article-title":"Pharmacology of Novel Synthetic Stimulants Structurally Related to the \"bath Salts\" Constituent 3,4-methylenedioxypyrovalerone (MDPV)","volume":"87","author":"Marusich","year":"2014","journal-title":"Neuropharmacology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.1111\/bph.13547","article-title":"Phase I Metabolites of Mephedrone Display Biological Activity as Substrates at Monoamine Transporters","volume":"173","author":"Mayer","year":"","journal-title":"Br. J. Pharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/7854_2016_63","article-title":"Application of a Combined Approach to Identify New Psychoactive Street Drugs and Decipher Their Mechanisms at Monoamine Transporters","author":"Mayer","year":"","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.brainres.2009.08.078","article-title":"Brain-derived Neurotrophic Factor and Cocaine Addiction","volume":"1314","author":"McGinty","year":"2010","journal-title":"Brain Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/7854_2016_18","article-title":"Decoding the Structure of Abuse Potential for New Psychoactive Substances: Structure-Activity Relationships for Abuse-Related Effects of 4-Substituted Methcathinone Analogs","volume":"32","author":"Negus","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B54","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos","year":"2004"},{"key":"B55","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1134\/S0006297917030099","article-title":"Neurotrophic Factors (BDNF and GDNF) and the Serotonergic System of the Brain","volume":"82","author":"Popova","year":"2017","journal-title":"Biochemistry (Mosc)"},{"key":"B56","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose Translation from Animal to Human Studies Revisited","volume":"22","author":"Reagan-Shaw","year":"2008","journal-title":"FASEB J."},{"key":"B57","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.neubiorev.2018.07.015","article-title":"Abuse potential and toxicity of the synthetic cathinones (i.e., \"Bath salts\")","volume":"110","author":"Riley","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B58","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00213-014-3632-0","article-title":"Effects of Acute and Repeated Cocaine on Markers for Neural Plasticity within the Mesolimbic System in Rats","volume":"232","author":"Rodriguez-Espinosa","year":"2015","journal-title":"Psychopharmacology (Berl)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/J.NEUROPHARM.2008.06.059","article-title":"Neurotrophic Factors and Structural Plasticity in Addiction","author":"Russo","year":"2009","journal-title":"Neuropharmacology"},{"key":"B60","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1007\/s00213-018-5075-5","article-title":"The Synthetic Cathinones, Butylone and Pentylone, Are Stimulants that Act as Dopamine Transporter Blockers but 5-HT Transporter Substrates","volume":"236","author":"Saha","year":"2019","journal-title":"Psychopharmacology (Berl)"},{"key":"B61","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1111\/j.1476-5381.2009.00267.x","article-title":"To Scale or Not to Scale: the Principles of Dose Extrapolation","volume":"157","author":"Sharma","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/0896-6273(90)90115-v","article-title":"Membrane Depolarization and Calcium Induce C-Fos Transcription via Phosphorylation of Transcription Factor CREB","volume":"4","author":"Sheng","year":"1990","journal-title":"Neuron"},{"key":"B63","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/7854_2016_20","article-title":"Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells","volume":"32","author":"Simmler","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.neuropharm.2013.11.008","article-title":"Monoamine Transporter and Receptor Interaction Profiles of a New Series of Designer Cathinones","volume":"79","author":"Simmler","year":"2014","journal-title":"Neuropharmacology"},{"key":"B65","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.tips.2014.11.006","article-title":"Amphetamines, New Psychoactive Drugs and the Monoamine Transporter Cycle","volume":"36","author":"Sitte","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1080\/15563650.2016.1271132","article-title":"Misuse of 2-(ethylamino)-1-(4-Methylphenyl)-1-Pentanone (4-MEAP), a Synthetic Cathinone","volume":"55","author":"Varma","year":"2017","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B67","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1021\/acschemneuro.8b00524","article-title":"Systematic Structure-Activity Studies on Selected 2-, 3-, and 4-Monosubstituted Synthetic Methcathinone Analogs as Monoamine Transporter Releasing Agents","volume":"10","author":"Walther","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1080\/15563650.2019.1591432","article-title":"Analytically Confirmed 4-Methyl-N-Ethylnorpentedrone (4-MEAP), a Synthetic Cathinone, in Cases Presenting to an Emergency Department","volume":"58","author":"Weng","year":"2020","journal-title":"Clin. Toxicol. (Phila)"},{"key":"B69","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.pharep.2019.05.011","article-title":"Induction of Immediate Early Genes Expression in the Mouse Striatum Following Acute Administration of Synthetic Cathinones","volume":"71","author":"Wojcieszak","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"B70","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/s11419-018-0409-x","article-title":"Effects of the New Generation \u03b1-pyrrolidinophenones on Spontaneous Locomotor Activities in Mice, and on Extracellular Dopamine and Serotonin Levels in the Mouse Striatum","volume":"36","author":"Wojcieszak","year":"2018","journal-title":"Forensic Toxicol."},{"key":"B71","unstructured":"Pentedrone: Critical Review Report2016"},{"key":"B72","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1073\/pnas.042693699","article-title":"The Brain-Derived Neurotrophic Factor Enhances Synthesis of Arc in Synaptoneurosomes","volume":"99","author":"Yin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1523\/JNEUROSCI.22-05-01532.2002","article-title":"Brain-derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation of Arc Synthesis","volume":"22","author":"Ying","year":"2002","journal-title":"J. Neurosci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/0361-9230(95)02005-C","article-title":"Roles of Dopamine D1 Receptors in Striatal Fos Protein Induction Associated with Methamphetamine Behavioral Sensitization in Rats","volume":"38","author":"Yoshida","year":"1995","journal-title":"Brain Res. Bull."},{"key":"B75","doi-asserted-by":"publisher","first-page":"268","DOI":"10.26355\/eurrev-201801-1412910.26355\/eurrev_201801_14129","article-title":"Synthetic Cathinones Related Fatalities: An Update","volume":"22","author":"Zaami","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1046\/j.1471-4159.2002.01089.x","article-title":"The Dopamine D1 Receptor Is a Critical Mediator for Cocaine-Induced Gene Expression","volume":"82","author":"Zhang","year":"2002","journal-title":"J. Neurochem."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.749429\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T01:17:08Z","timestamp":1635211028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.749429\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":76,"alternative-id":["10.3389\/fphar.2021.749429"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.749429","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]},"article-number":"749429"}}