{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:50:55Z","timestamp":1793836255622,"version":"4.6.1"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UAE University\u2019s Office of Graduate Studies and Research","award":["21M132"],"award-info":[{"award-number":["21M132"]}]},{"name":"UAE University\u2019s Office of Graduate Studies and Research","award":["12M099"],"award-info":[{"award-number":["12M099"]}]},{"name":"Zayed-Center for Health Sciences","award":["21M132"],"award-info":[{"award-number":["21M132"]}]},{"name":"Zayed-Center for Health Sciences","award":["12M099"],"award-info":[{"award-number":["12M099"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Based on their proven anti-inflammatory and antioxidant effects, recent studies have examined the therapeutic potential of the sodium-glucose cotransporter 2 (SGLT2) inhibitors in neurodevelopmental disorders such as autism spectrum disorder (ASD). Therefore, the aim of this study is to assess the effects of subchronic systemic treatment with intraperitoneal (i.p.) canagliflozin (20, 50, and 100 mg\/kg) compared to aripiprazole (ARP) (3 mg\/g, i.p.) in a valproic acid (VPA)-induced rat model of autism. The behavioral characteristics of ASD, oxidative stress, and acetylcholinesterase (AChE) activity in rats with ASD-like behaviors, which were induced by prenatal exposure to VPA, were evaluated. The behavioral assessment methods used for this study were the open field test (OFT), the marble-burying test (MBT), and the nestlet-shredding test (NST) to examine their exploratory, anxiety, and compulsiveness-like actions, while the biochemical assessment used for this study was an ELISA colorimetric assay to measure ASD biomarker activity in the hippocampus, prefrontal cortex, and cerebellum. Rats that were pretreated with 100 mg\/kg of canagliflozin displayed a significantly lower percentage of shredding (1.12 \u00b1 0.6%, p &lt; 0.01) compared to the ARP group (3.52 \u00b1 1.6%). Pretreatment with (20 mg\/kg, 50 mg\/kg, and 100 mg\/kg) canagliflozin reversed anxiety levels and hyperactivity and reduced hyper-locomotor activity significantly (161 \u00b1 34.9 s, p &lt; 0.05; 154 \u00b1 44.7 s, p &lt; 0.05; 147 \u00b1 33.6 s, p &lt; 0.05) when compared with the VPA group (303 \u00b1 140 s). Moreover, canagliflozin and ARP mitigated oxidative stress status by restoring levels of glutathione (GSH) and catalase (CAT) and increasing the levels of malondialdehyde (MDA) in all tested brain regions. The observed results propose repurposing of canagliflozin in the therapeutic management of ASD. However, further investigations are still required to verify the clinical relevance of canagliflozin in ASD.<\/jats:p>","DOI":"10.3390\/ph16050769","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:35:11Z","timestamp":1684492511000},"page":"769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Canagliflozin Ameliorates Oxidative Stress and Autistic-like Features in Valproic-Acid-Induced Autism in Rats: Comparison with Aripiprazole Action"],"prefix":"10.3390","volume":"16","author":[{"given":"Mohammed Moutaz","family":"Nakhal","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Sciences, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petrilla","family":"Jayaprakash","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salahdein","family":"Aburuz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Zayed Center for Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 17666, United Arab Emirates"},{"name":"Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0320-1487","authenticated-orcid":false,"given":"Bassem","family":"Sadek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Zayed Center for Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 17666, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2789-8514","authenticated-orcid":false,"given":"Amal","family":"Akour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates"},{"name":"Zayed Center for Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 17666, United Arab Emirates"},{"name":"Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2013.12.001","article-title":"Developmental pathways to autism: A review of prospective studies of infants at risk","volume":"39","author":"Jones","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.annepidem.2007.10.013","article-title":"Prevalence and characteristics of children with autism-spectrum disorders","volume":"18","author":"Nicholas","year":"2008","journal-title":"Ann. Epidemiol."},{"key":"ref_3","first-page":"e3901","article-title":"Where is the evidence? A narrative literature review of the treatment modalities for autism spectrum disorders","volume":"11","author":"Medavarapu","year":"2019","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3109\/09637486.2013.832171","article-title":"Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well as protein levels of drebrin and transthyretin in mice: An exploratory study","volume":"65","author":"Varamini","year":"2014","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Indika, N.L., Frye, R.E., Rossignol, D.A., Owens, S.C., Senarathne, U.D., Grabrucker, A.M., Perera, R., Engelen, M.P., and Deutz, N.E. (2023). The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder. J. Pers. Med., 13.","DOI":"10.3390\/jpm13020252"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/aur.239","article-title":"Global prevalence of autism and other pervasive developmental disorders","volume":"5","author":"Elsabbagh","year":"2012","journal-title":"Autism Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/jhg.2017.91","article-title":"The pharmacogenomics of valproic acid","volume":"62","author":"Zhu","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000509109","article-title":"A systematic review of the valproic-acid-induced rodent model of autism","volume":"42","author":"Chaliha","year":"2020","journal-title":"Dev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S2213-8587(17)30314-5","article-title":"SGLT2 inhibitors: Hypotheses on the mechanism of cardiovascular protection","volume":"6","author":"Bell","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/s41569-020-0406-8","article-title":"SGLT2 inhibitors: Mechanisms of cardiovascular benefit beyond glycaemic control","volume":"17","author":"Cowie","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"45","author":"Davies","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kolesnik, E., Scherr, D., Rohrer, U., Benedikt, M., Manninger, M., Sourij, H., and von Lewinski, D. (2022). SGLT2 inhibitors and their antiarrhythmic properties. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031678"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.ajkd.2018.03.022","article-title":"SGLT2 inhibition for the prevention and treatment of diabetic kidney disease: A review","volume":"72","author":"Alicic","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nakhal, M.M., Aburuz, S., Sadek, B., and Akour, A. (2022). Repurposing SGLT2 Inhibitors for Neurological Disorders: A Focus on the Autism Spectrum Disorder. Molecules, 27.","DOI":"10.3390\/molecules27217174"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1002\/jcb.26036","article-title":"Molecular interaction of anti-diabetic drugs with acetylcholinesterase and sodium glucose co-transporter 2","volume":"118","author":"Shakil","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_17","first-page":"1216","article-title":"Prediction of anti-diabetic drugs as dual inhibitors against acetylcholinesterase and beta-secretase: A neuroinformatics study","volume":"15","author":"Shaikh","year":"2016","journal-title":"CNS Neurol. Disord.-Drug Targets (Former. Curr. Drug Targets-CNS Neurol. Disord.)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9388562","DOI":"10.1155\/2021\/9388562","article-title":"Investigating the effects of dapagliflozin on cardiac function, inflammatory response, and cardiovascular outcome in patients with STEMI complicated with T2DM after PCI","volume":"2021","author":"Xue","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"173040","DOI":"10.1016\/j.ejphar.2020.173040","article-title":"Empagliflozin ameliorates endothelial dysfunction and suppresses atherogenesis in diabetic apolipoprotein E-deficient mice","volume":"875","author":"Ganbaatar","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/j.ekir.2021.05.022","article-title":"Markers of kidney injury, inflammation, and fibrosis associated with ertugliflozin in patients with CKD and diabetes","volume":"6","author":"Liu","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12933-019-0828-y","article-title":"Sotagliflozin, the first dual SGLT inhibitor: Current outlook and perspectives","volume":"18","author":"Cefalo","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14659","DOI":"10.1038\/s41598-020-71599-2","article-title":"Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK\u2013Akt\u2013eNOS pathway in the isoprenaline-induced oxidative stress model","volume":"10","author":"Hasan","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zaibi, N., Li, P., and Xu, S.Z. (2021). Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247234"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Iannantuoni, F.M., de Mara\u00f1on, A., Diaz-Morales, N., Falcon, R., Ba\u00f1uls, C., Abad-Jimenez, Z., Victor, V.M., Hernandez-Mijares, A., and Rovira-Llopis, S. (2019). The SGLT2 inhibitor empagliflozin ameliorates the inflammatory profile in type 2 diabetic patients and promotes an antioxidant response in leukocytes. J. Clin. Med., 8.","DOI":"10.3390\/jcm8111814"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e019995","DOI":"10.1161\/JAHA.120.019995","article-title":"Effects of sodium-glucose linked transporter 2 inhibition with ertugliflozin on mitochondrial function, energetics, and metabolic gene expression in the presence and absence of diabetes mellitus in mice","volume":"10","author":"Croteau","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/dom.14864","article-title":"Mechanisms underlying the blood pressure-lowering effects of empagliflozin, losartan and their combination in people with type 2 diabetes: A secondary analysis of a randomized crossover trial","volume":"25","author":"Scholtes","year":"2023","journal-title":"Diabetes Obes. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110821","DOI":"10.1016\/j.biopha.2020.110821","article-title":"Sodium-glucose co-transporter-2 (SGLT-2) inhibition reduces glucose uptake to induce breast cancer cell growth arrest through AMPK\/mTOR pathway","volume":"132","author":"Zhou","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.2337\/db19-0991","article-title":"Empagliflozin ameliorates obesity-related cardiac dysfunction by regulating Sestrin2-mediated AMPK-mTOR signaling and redox homeostasis in high-fat diet\u2013induced obese mice","volume":"69","author":"Sun","year":"2020","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"ehab724.3289","DOI":"10.1093\/eurheartj\/ehab724.3289","article-title":"The SGLT2 inhibitor ertugliflozin causes a switch of cardiac substrate utilization leading to reduced cardiac mTOR-signaling, unfolded protein response and apoptosis","volume":"42","author":"Moellmann","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Eissa, N., Azimullah, S., Jayaprakash, P., Jayaraj, R.L., Reiner, D., Ojha, S.K., Beiram, R., Stark, H., \u0141a\u017cewska, D., and Kie\u0107-Kononowicz, K. (2020). The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 alleviates autistic-like behaviors and oxidative stress in valproic acid induced autism in mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113996"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0031-9384(96)00445-3","article-title":"Behavioral and adrenocortical responses to open-field test in rats selected for reduced aggressiveness toward humans","volume":"61","author":"Plyusnina","year":"1997","journal-title":"Physiol. Behav."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/ijnp\/pyy043","article-title":"Motor impairments correlate with social deficits and restricted neuronal loss in an environmental model of autism","volume":"21","author":"Haida","year":"2018","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Angoa-P\u00e9rez, M., Kane, M.J., Briggs, D.I., Francescutti, D.M., and Kuhn, D.M. (2013). Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice. J. Vis. Exp. JoVE.","DOI":"10.3791\/50978-v"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1007\/s12035-019-01742-2","article-title":"Oxidative stress in autism spectrum disorder","volume":"57","author":"Meguid","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jayaprakash, P., Isaev, D., Shabbir, W., Lorke, D.E., Sadek, B., and Oz, M. (2021). Curcumin potentiates \u03b17 nicotinic acetylcholine receptors and alleviates autistic-like social deficits and brain oxidative stress status in mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147251"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Eissa, N., Venkatachalam, K., Jayaprakash, P., Falkenstein, M., Dubiel, M., Frank, A., Reiner-Link, D., Stark, H., and Sadek, B. (2021). The multi-targeting ligand ST-2223 with histamine H3 receptor and dopamine D2\/D3 receptor antagonist properties mitigates autism-like repetitive behaviors and brain oxidative stress in mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041947"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1038\/sj.npp.1300983","article-title":"Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: Comparing aripiprazole to other antipsychotics in animal models","volume":"31","author":"Natesan","year":"2006","journal-title":"Neuropsychopharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/npp.2009.201","article-title":"Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP","volume":"35","author":"Silverman","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"136354","DOI":"10.1016\/j.neulet.2021.136354","article-title":"Effects of clozapine and risperidone antipsychotic drugs on the expression of CACNA1C and behavioral changes in rat \u2018Ketamine model of schizophrenia","volume":"770","author":"Sanavi","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6711160","DOI":"10.1155\/2022\/6711160","article-title":"Metformin alleviates autistic-like behaviors elicited by high-fat diet consumption and modulates the crosstalk between serotonin and gut microbiota in mice","volume":"2022","author":"Deng","year":"2022","journal-title":"Behav. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Estaphan, S., Curp\u0103n, A.S., Khalifa, D., Rashed, L., Ciobica, A., Cantemir, A., Ciobica, A., Trus, C., Ali, M., and ShamsEldeen, A. (2021). Combined Low Dose of Ketamine and Social Isolation: A Possible Model of Induced Chronic Schizophrenia-Like Symptoms in Male Albino Rats. Brain Sci., 11.","DOI":"10.3390\/brainsci11070917"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/fcp.12548","article-title":"Empagliflozin attenuates transient cerebral ischemia\/reperfusion injury in hyperglycemic rats via repressing oxidative\u2013inflammatory\u2013apoptotic pathway","volume":"34","author":"Amin","year":"2020","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1007\/s11064-007-9289-x","article-title":"Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain","volume":"32","author":"Eren","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08923973.2022.2143371","article-title":"Neuroprotective effect of canagliflozin against cisplatin-induced cerebral cortex injury is mediated by regulation of HO-1\/PPAR-\u03b3, SIRT1\/FOXO-3, JNK\/AP-1, TLR4\/iNOS, and Ang II\/Ang 1\u20137 signals","volume":"10","author":"Hassanein","year":"2022","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s11064-012-0717-1","article-title":"Bacopa monniera (L.) Wettst ameliorates behavioral alterations and oxidative markers in sodium valproate induced autism in rats","volume":"37","author":"Sandhya","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cbi.2017.08.013","article-title":"Canagliflozin prevents scopolamine-induced memory impairment in rats: Comparison with galantamine hydrobromide action","volume":"277","author":"Arafa","year":"2017","journal-title":"Chem. -Biol. Interact."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fphar.2023.1113966","article-title":"Canagliflozin Alleviates Valproic Acid-induced Rat Autism: The Role of PTEN\/PDK\/PPAR-\u03b3 signaling pathways","volume":"14","author":"Elgamal","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"214","DOI":"10.9758\/cpn.2018.16.2.214","article-title":"Early postnatal valproic acid exposure increase the protein level of astrocyte markers in frontal cortex of rat","volume":"16","author":"Mony","year":"2018","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"338","DOI":"10.9758\/cpn.2016.14.4.338","article-title":"Valproic acid exposure during early postnatal gliogenesis leads to autistic-like behaviors in rats","volume":"14","author":"Mony","year":"2016","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S6188","DOI":"10.4137\/JCNSD.S6188","article-title":"Animal models of autism: An epigenetic and environmental viewpoint","volume":"2","author":"Iwata","year":"2010","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1007\/s10826-021-01905-7","article-title":"Gender Differences in Treatment-Seeking Youth with Autism Spectrum Disorder","volume":"30","author":"Cariveau","year":"2021","journal-title":"J. Child Fam. Stud."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_53","first-page":"10","article-title":"Comparative renal protective effects of canagliflozin and telmisartan in a rat model of diabetic nephropathy","volume":"2","author":"Mahmoud","year":"2016","journal-title":"J. Nephrol. Renal. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Solares-Pascasio, J.I., Ceballos, G., Calzada, F., Barbosa, E., and Velazquez, C. (2021). Antihyperglycemic and lipid profile effects of Salvia amarissima Ortega on streptozocin-induced type 2 diabetic mice. Molecules, 26.","DOI":"10.3390\/molecules26040947"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.jtcme.2022.03.003","article-title":"Formulation and evaluation of SGLT2 inhibitory effect of a polyherbal mixture inspired from Ayurvedic system of medicine","volume":"12","author":"Kumar","year":"2022","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1369-1600.2010.00223.x","article-title":"Attenuation of reinforcing and psychomotor stimulant effects of amphetamine by aripiprazole","volume":"16","year":"2011","journal-title":"Addict. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s00213-018-4874-z","article-title":"Effects of cariprazine on extracellular levels of glutamate, GABA, dopamine, noradrenaline and serotonin in the medial prefrontal cortex in the rat phencyclidine model of schizophrenia studied by microdialysis and simultaneous recordings of locomotor activity","volume":"235","author":"Kehr","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_58","first-page":"9","article-title":"Characterization of four types of tail abnormalities in rats treated prenatally with valproic acid","volume":"5","author":"Saft","year":"2014","journal-title":"Eneurobiolog\u00eda"},{"key":"ref_59","first-page":"1431","article-title":"The laboratory rat: Age and body weight matter","volume":"20","author":"Ghasemi","year":"2021","journal-title":"EXCLI J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s10803-019-03927-z","article-title":"The effects of early intervention on social communication outcomes for children with autism spectrum disorder: A meta-analysis","volume":"50","author":"Fuller","year":"2020","journal-title":"J. Autism Dev. Disord."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s12640-020-00169-1","article-title":"Oxiracetam and zinc ameliorates autism-like symptoms in propionic acid model of rats","volume":"37","author":"Paudel","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41386-018-0098-5","article-title":"Pharmacological modulation of AMPA receptor rescues social impairments in animal models of autism","volume":"44","author":"Kim","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.51248\/.v41i1.526","article-title":"A systematic review on Valproate induced rat model of autism: Pathophysiology, treatment, developmental and neurobehavioral assessment of rat offsprings","volume":"41","author":"Kavitha","year":"2021","journal-title":"Biomedicine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"113432","DOI":"10.1016\/j.physbeh.2021.113432","article-title":"Implication of the social function of excessive self-grooming behavior in BTBR T+ ltpr3tf\/J mice as an idiopathic model of autism","volume":"237","author":"Arakawa","year":"2021","journal-title":"Physiol. Behav."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lazic, S.E. (2015). Analytical strategies for the marble burying test: Avoiding impossible predictions and invalid p-values. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1062-7"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"108775","DOI":"10.1016\/j.cbi.2019.108775","article-title":"The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammmation in sodium valproate induced autism in mice","volume":"312","author":"Eissa","year":"2019","journal-title":"Chem.-Biol. Interact."},{"key":"ref_67","first-page":"e3564","article-title":"Whole animal perfusion fixation for rodents","volume":"30","author":"Gage","year":"2012","journal-title":"JoVE (J. Vis. Exp.)"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2147\/DDDT.S144730","article-title":"Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice","volume":"12","author":"Bastaki","year":"2018","journal-title":"Drug Des. Dev. Ther."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/769\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:38:47Z","timestamp":1760125127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":68,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ph16050769"],"URL":"https:\/\/doi.org\/10.3390\/ph16050769","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}