{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:44:03Z","timestamp":1790905443808,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lublin","award":["DS 22\/21"],"award-info":[{"award-number":["DS 22\/21"]}]},{"name":"private grant","award":["DS 22\/21"],"award-info":[{"award-number":["DS 22\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Maternal separation (MS) is a key contributor to neurodevelopmental disorders, including learning disabilities. To test the hypothesis that dopamine signaling is a major factor in this, an atypical new dopamine transporter (DAT) inhibitor, CE-123, was assessed for its potential to counteract the MS-induced spatial learning and memory deficit in male and female rats. Hence, neonatal rats (postnatal day (PND)1 to 21) were exposed to MS (180 min\/day). Next, the acquisition of spatial learning and memory (Barnes maze task) and the expression of dopamine D1 receptor, dopamine transporter (DAT), and the neuronal GTPase, RIT2, which binds DAT in the vehicle-treated rats were evaluated in the prefrontal cortex and hippocampus in the adolescent animals. The results show that MS impairs the acquisition of spatial learning and memory in rats, with a more severe effect in females. Moreover, the MS induced upregulation of DAT and dopamine D1 receptors expression in the prefrontal cortex and hippocampus in adolescent rats. Regarding RIT2, the expression was decreased in the hippocampus for both the males and females, however, in the prefrontal cortex, reduction was found only in the females, suggesting that there are region-specific differences in DAT endocytic trafficking. CE-123 ameliorated the behavioral deficits associated with MS. Furthermore, it decreased the MS-induced upregulation of D1 receptor expression level in the hippocampus. These effects were more noted in females. Overall, CE-123, an atypical DAT inhibitor, is able to restore cognitive impairment and dopamine signaling in adolescent rats exposed to MS\u2014with more evident effect in females than males.<\/jats:p>","DOI":"10.3390\/ijms231810718","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T23:16:36Z","timestamp":1663197396000},"page":"10718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Novel Dopamine Transporter Inhibitor, CE-123, Ameliorates Spatial Memory Deficits Induced by Maternal Separation in Adolescent Rats: Impact of Sex"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-3645","authenticated-orcid":false,"given":"Pawel","family":"Grochecki","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-8181","authenticated-orcid":false,"given":"Irena","family":"Smaga","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2246-3108","authenticated-orcid":false,"given":"Paulina","family":"Surowka","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-9131","authenticated-orcid":false,"given":"Marta","family":"Marszalek-Grabska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8B, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Predrag","family":"Kalaba","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, 1010 Vienna, Austria"},{"name":"Paracelsus Private Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Dragacevic","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, 1010 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Kotlinska","sequence":"additional","affiliation":[{"name":"Department of Neurology, SP ZOZ MSWiA Hospital, 35-111 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-7942","authenticated-orcid":false,"given":"Malgorzata","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Lubec","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, 1010 Vienna, Austria"},{"name":"Paracelsus Private Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-1515","authenticated-orcid":false,"given":"Jolanta H.","family":"Kotlinska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/nrn2639","article-title":"Effects of stress throughout the lifespan on the brain, behaviour and cognition","volume":"10","author":"Lupien","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0006-8993(02)02985-2","article-title":"Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats","volume":"950","author":"Huot","year":"2002","journal-title":"Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0149-7634(03)00008-3","article-title":"Early experience as a determinant of adult behavioural responses to reward: The effects of repeated maternal separation in the rat","volume":"27","author":"Matthews","year":"2003","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0143-4179(03)00043-X","article-title":"Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats","volume":"37","author":"Ploj","year":"2003","journal-title":"Neuropeptides"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/FBP.0000000000000388","article-title":"Exposure to opiates in male adolescent rats alters pain perception in the male offspring","volume":"29","author":"Pachenari","year":"2018","journal-title":"Behav. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1080\/09658211.2018.1561897","article-title":"The relationship between early life stress and working memory in adulthood: A systematic review and meta-analysis","volume":"27","author":"Goodman","year":"2019","journal-title":"Memory"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00213-010-2009-2","article-title":"Effects of early life stress on cognitive and affective function: An integrated review of human literature","volume":"214","author":"Pechtel","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Paterniti, S., Sterner, I., Caldwell, C., and Bisserbe, J.C. (2017). Childhood neglect predicts the course of major depression in a tertiary care sample: A follow-up study. BMC Psychiatry, 17.","DOI":"10.1186\/s12888-017-1270-x"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0031-9384(98)00300-X","article-title":"Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats","volume":"66","author":"Wigger","year":"1999","journal-title":"Physiol. Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0091-3057(02)00781-5","article-title":"Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats","volume":"73","author":"Kalinichev","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbr.2011.04.015","article-title":"Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization","volume":"223","author":"Muhammad","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tsuda, M.C., and Ogawa, S. (2012). Long-lasting consequences of neonatal maternal separation on social behaviors in ovariectomized female mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033028"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1017\/S1461145710001239","article-title":"Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders","volume":"14","author":"Niwa","year":"2011","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.dcn.2015.09.005","article-title":"Early maternal separation impacts cognitive flexibility at the age of first independence in mice","volume":"18","author":"Thomas","year":"2016","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0163-1047(05)80065-2","article-title":"Memory for spatial location as a function of temporal lag in rats: Role of hippocampus and medial prefrontal cortex","volume":"61","author":"Chiba","year":"1994","journal-title":"Behav. Neural. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/297681a0","article-title":"Place navigation impaired in rats with hippocampal lesions","volume":"297","author":"Morris","year":"1982","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.biopsych.2014.04.016","article-title":"Interaction of early life stress and corticotropin-releasing hormone receptor gene: Effects on working memory","volume":"76","author":"Fuge","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/(SICI)1098-1063(1999)9:4<352::AID-HIPO3>3.0.CO;2-1","article-title":"Do hippocampal pyramidal cells signal non-spatial as well as spatial information?","volume":"9","year":"1999","journal-title":"Hippocampus"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1113\/jphysiol.2009.172445","article-title":"What is remembered? Role of attention on the encoding and retrieval of hippocampal representations","volume":"587","author":"Muzzio","year":"2009","journal-title":"J. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0896-6273(04)00192-8","article-title":"Increased attention to spatial context increases both place field stability and spatial memory","volume":"42","author":"Kentros","year":"2004","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/0306-4522(96)00202-3","article-title":"Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat","volume":"74","author":"Gasbarri","year":"1996","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1523\/JNEUROSCI.20-04-01568.2000","article-title":"Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction","volume":"20","author":"Mizoguchi","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/j.celrep.2016.01.070","article-title":"Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the hippocampus","volume":"14","author":"Broussard","year":"2016","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/cercor\/bhs362","article-title":"Dopamine D1\/D5 receptors mediate informational saliency that promotes persistent hippocampal long-term plasticity","volume":"24","author":"Hansen","year":"2014","journal-title":"Cereb. Cortex."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14835","DOI":"10.1073\/pnas.1616515114","article-title":"Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory","volume":"113","author":"Kempadoo","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","first-page":"37","article-title":"Insights into the role of dopamine receptor systems in learning and memory","volume":"18","author":"George","year":"2007","journal-title":"Rev. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.nlm.2012.01.005","article-title":"D1\/D5 dopamine receptors modulate spatial memory formation","volume":"97","author":"Radiske","year":"2012","journal-title":"Neurobiol. Learn Mem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.neuroscience.2010.06.034","article-title":"Dopamine D1 but not D3 receptor is critical for spatial learning and related signaling in the hippocampus","volume":"169","author":"Xing","year":"2010","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nn.4231","article-title":"PV plasticity sustained through D1\/5 dopamine signaling required for long-term memory consolidation","volume":"19","author":"Karunakaran","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.neuroscience.2005.09.028","article-title":"Under the curve: Critical issues for elucidating D1 receptor function in working memory","volume":"139","author":"Williams","year":"2006","journal-title":"Neuroscience"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/hipo.22143","article-title":"Dopamine D1 receptor activity modulates object recognition memory consolidation in the perirhinal cortex but not in the hippocampus","volume":"23","author":"Balderas","year":"2013","journal-title":"Hippocampus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbr.2006.03.026","article-title":"D1 receptor modulation of memory retrieval performance is associated with changes in pCREB and pDARPP-32 in rat prefrontal cortex","volume":"171","author":"Hotte","year":"2006","journal-title":"Behav. Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.nlm.2013.07.012","article-title":"Consolidation of object recognition memory requires simultaneous activation of dopamine D1\/D5 receptors in the amygdala and medial prefrontal cortex but not in the hippocampus","volume":"106","author":"Rossato","year":"2013","journal-title":"Neurobiol. Learn Mem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1124\/pr.108.000869","article-title":"SLC6 neurotransmitter transporters: Structure, function, and regulation","volume":"63","author":"Kristensen","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0165-0173(97)00063-5","article-title":"Re-evaluation of the role of the dopamine transporter in dopamine system homeostasis","volume":"26","author":"Gainetdinov","year":"1998","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"112642","DOI":"10.1016\/j.bbr.2020.112642","article-title":"Deficit in working memory and abnormal behavioral tactics in dopamine transporter knockout rats during training in the 8-arm maze","volume":"390","author":"Kurzina","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3109\/01677063.2016.1144751","article-title":"Dopamine transporter mutant animals: A translational perspective","volume":"30","author":"Efimova","year":"2016","journal-title":"J. Neurogenet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/j.euroneuro.2015.07.028","article-title":"Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review","volume":"25","author":"Battleday","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.schres.2011.05.015","article-title":"The effect of adjunctive armodafinil on cognitive performance and psychopathology in antipsychotic-treated patients with schizophrenia\/schizoaffective disorder: A randomized, double-blind, placebo-controlled trial","volume":"130","author":"Bobo","year":"2011","journal-title":"Schizophr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00213-017-4650-5","article-title":"Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects","volume":"235","author":"Dolder","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s11011-018-0190-x","article-title":"Haloperidol attenuates methylphenidate and modafinil induced behavioural sensitization and cognitive enhancement","volume":"33","author":"Alam","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0149-7634(97)00020-1","article-title":"Modulation of the induction or expression of psychostimulant sensitization by the circumstances surrounding drug administration","volume":"22","author":"Robinson","year":"1998","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_43","first-page":"349","article-title":"Mechanisms of modafinil: A review of current research","volume":"3","author":"Gerrard","year":"2007","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9330","DOI":"10.1021\/acs.jmedchem.7b01313","article-title":"Heterocyclic analogues of modafinil as novel, atypical dopamine transporter inhibitors","volume":"60","author":"Kalaba","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1021\/acs.jmedchem.9b01938","article-title":"Structure-activity relationships of novel thiazole-based modafinil analogues acting at monoamine transporters","volume":"63","author":"Kalaba","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fnbeh.2017.00222","article-title":"A novel dopamine transporter inhibitor CE-123 improves cognitive flexibility and maintains impulsivity in healthy male rats","volume":"11","author":"Nikiforuk","year":"2017","journal-title":"Front. Behav. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bbr.2018.01.032","article-title":"A daily single dose of a novel modafinil analogue CE-123 improves memory acquisition and memory retrieval","volume":"343","author":"Kristofova","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113326","DOI":"10.1016\/j.bbr.2021.113326","article-title":"CE-123, a novel dopamine transporter inhibitor, attenuates locomotor hyperactivity and improves cognitive functions in rat model of fetal alcohol spectrum disorders","volume":"410","author":"Korz","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sagheddu, C., Pintori, N., Kalaba, P., Draga\u010devi\u0107, V., Piras, G., Lubec, J., Simola, N., De Luca, M.A., Lubec, G., and Pistis, M. (2020). Neurophysiological and neurochemical effects of the putative cognitive enhancer (S)-CE-123 on mesocorticolimbic dopamine system. Biomolecules, 10.","DOI":"10.3390\/biom10050779"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6784","DOI":"10.1523\/JNEUROSCI.16-21-06784.1996","article-title":"Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of ras proteins","volume":"16","author":"Lee","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13758","DOI":"10.1523\/JNEUROSCI.2649-11.2011","article-title":"The plasma membrane-associated GTPase Rin interacts with the dopamine transporter and is required for protein kinase C-regulated dopamine transporter trafficking","volume":"31","author":"Navaroli","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5229","DOI":"10.1074\/jbc.RA120.012628","article-title":"Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact","volume":"295","author":"Fagan","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/j.neuroscience.2010.06.035","article-title":"Early stress exposure impairs synaptic potentiation in the rat medial prefrontal cortex underlying contextual fear extinction","volume":"169","author":"Judo","year":"2010","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"78970","DOI":"10.1155\/2007\/78970","article-title":"Stress and memory: Behavioral effects and neurobiological mechanisms","volume":"2007","author":"Sandi","year":"2007","journal-title":"Neural. Plast."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/j.neurobiolaging.2014.01.024","article-title":"Maternal separation impairs long term-potentiation in CA1-CA3 synapses and hippocampal-dependent memory in old rats","volume":"35","author":"Sousa","year":"2014","journal-title":"Neurobiol. Aging."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"572224","DOI":"10.3389\/fpsyt.2020.572224","article-title":"Early-life neglect alters emotional and cognitive behavior in a sex-dependent manner and reduces glutamatergic neuronal excitability in the prefrontal cortex","volume":"11","author":"Sun","year":"2021","journal-title":"Front Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Filarowska-Jurko, J., Komsta, L., Smaga, I., Surowka, P., Marszalek-Grabska, M., Grochecki, P., Nizio, D., Filip, M., and Kotlinska, J.H. (2022). Maternal separation alters ethanol drinking and reversal learning processes in adolescent rats: The impact of sex and glycine transporter type 1 (GlyT1) inhibitor. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105350"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Oomen, C.A., Girardi, C.E., Cahyadi, R., Verbeek, E.C., Krugers, H., Jo\u00ebls, M., and Lucassen, P.J. (2009). Opposite effects of early maternal deprivation on neurogenesis in male versus female rats. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0003675"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fendo.2014.00013","article-title":"Age- and sex-dependent effects of early life stress on hippocampal neurogenesis","volume":"5","author":"Loi","year":"2014","journal-title":"Front. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1016\/j.neubiorev.2012.07.003","article-title":"Early life manipulations alter learning and memory in rats","volume":"36","author":"Kosten","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.neubiorev.2017.05.021","article-title":"Experience-induced transgenerational (re-)programming of neuronal structure and functions: Impact of stress prior and during pregnancy","volume":"117","author":"Braun","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.biopsych.2015.02.036","article-title":"Stress in utero: Prenatal programming of brain plasticity and cognition","volume":"78","author":"Bock","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000448055","article-title":"The impact of parent-infant interaction on epigenetic plasticity mediating synaptic adaptations in the infant brain","volume":"49","author":"Matas","year":"2016","journal-title":"Psychopathology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s00429-013-0688-2","article-title":"Early life stress and sex-specific sensitivity of the catecholaminergic systems in prefrontal and limbic regions of Octodon degus","volume":"220","author":"Kunzler","year":"2015","journal-title":"Brain Struct. Funct."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0306-4522(03)00123-4","article-title":"Mother\u2019s voice \u201cbuffers\u201d separation-induced receptor changes in the prefrontal cortex of octodon degus","volume":"119","author":"Ziabreva","year":"2003","journal-title":"Neuroscience"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kasanova, Z., Hernaus, D., Vaessen, T., van Amelsvoort, T., Winz, O., Heinzel, A., Pruessner, J., Mottaghy, F.M., Collip, D., and Myin-Germeys, I. (2016). Early-life stress affects stress-related prefrontal dopamine activity in healthy adults, but not in individuals with psychotic disorder. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150746"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ijdevneu.2017.01.001","article-title":"The effects of early-life stress on dopamine system function in adolescent female rats","volume":"57","author":"Solarz","year":"2017","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.neuropharm.2019.03.001","article-title":"A novel dopamine D1 receptor agonist excites delay-dependent working memory-related neuronal firing in primate dorsolateral prefrontal cortex","volume":"150","author":"Wang","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbr.2013.01.040","article-title":"Early maternal deprivation-induced modifications in the neurobiological, neurochemical and behavioral profile of adult rats","volume":"244","author":"Rentesi","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/10253890.2020.1777974","article-title":"Early life stress due to repeated maternal separation alters the working memory acquisition brain functional network","volume":"24","author":"Banqueri","year":"2021","journal-title":"Stress"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.bbrc.2006.11.104","article-title":"Hyperactivity and alteration of the midbrain dopaminergic system in maternally stressed male mice offspring","volume":"352","author":"Son","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.biopsych.2013.04.023","article-title":"Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates","volume":"74","author":"Converse","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/j.1467-8624.2004.00727.x","article-title":"High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds","volume":"75","author":"Marcoen","year":"2004","journal-title":"Child Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/jpepsy\/jsm005","article-title":"Attention-deficit\/hyperactivity disorder: Diagnosis, lifespan, comorbidities, and neurobiology","volume":"32","author":"Spencer","year":"2007","journal-title":"J. Pediatr. Psychol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1001\/jama.2009.1308","article-title":"Evaluating dopamine reward pathway in ADHD: Clinical implications","volume":"302","author":"Volkow","year":"2009","journal-title":"JAMA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.taap.2004.08.013","article-title":"The dopamine transporter: Role in neurotoxicity and human disease","volume":"204","author":"Bannon","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1586\/14737175.6.4.455","article-title":"A review of the use of modafinil for attention-deficit hyperactivity disorder","volume":"6","author":"Turner","year":"2006","journal-title":"Expert Rev. Neurother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/s41386-019-0457-x","article-title":"Conditional, inducible gene silencing in dopamine neurons reveals a sex-specific role for Rit2 GTPase in acute cocaine response and striatal function","volume":"45","author":"Sweeney","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/S1734-1140(10)70385-6","article-title":"Impact of maternal separation on neural cell adhesion molecules expression in dopaminergic brain regions of juvenile, adolescent and adult rats","volume":"62","author":"Chocyk","year":"2010","journal-title":"Pharmacol. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Grochecki, P., Smaga, I., Lopatynska-Mazurek, M., Gibula-Tarlowska, E., Kedzierska, E., Listos, J., Talarek, S., Marszalek-Grabska, M., Hubalewska-Mazgaj, M., and Korga-Plewko, A. (2021). Effects of mephedrone and amphetamine exposure during adolescence on spatial memory in adulthood: Behavioral and neurochemical analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020589"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lopatynska-Mazurek, M., Antolak, A., Grochecki, P., Gibula-Tarlowska, E., Bodzon-Kulakowska, A., Listos, J., Kedzierska, E., Suder, P., Silberring, J., and Kotlinska, J.H. (2021). Rapamycin improves spatial learning deficits, vulnerability to alcohol addiction and altered expression of the GluN2B subunit of the NMDA receptor in adult rats exposed to ethanol during the neonatal period. Biomolecules, 11.","DOI":"10.3390\/biom11050650"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1101\/lm.334306","article-title":"Spatial and nonspatial escape strategies in the Barnes maze","volume":"13","author":"Harrison","year":"2006","journal-title":"Learn Mem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bbr.2014.01.047","article-title":"The differential hippocampal phosphoproteome of Apodemus sylvaticus paralleling spatial memory retrieval in the Barnes maze","volume":"264","author":"Li","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbr.2017.10.007","article-title":"ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from \u2018binge-like\u2019 ethanol exposure in rats","volume":"338","author":"Suder","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00210-018-1589-y","article-title":"Assessment of spatial learning and memory in the Barnes maze task in rodents-methodological consideration","volume":"392","author":"Gawel","year":"2019","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10718\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:31:21Z","timestamp":1760142681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,14]]},"references-count":85,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810718"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810718","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,14]]}}}