{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T16:45:22Z","timestamp":1771692322435,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS 22\/2020"],"award-info":[{"award-number":["DS 22\/2020"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1.5 g\/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 and 10 mg\/kg) was given before intragastric ethanol (5 g\/kg\/day) administration at postnatal day (PND)4\u20139 (an equivalent to the third trimester of human pregnancy). Spatial memory\/reversal learning and rewarding ethanol effect were evaluated in adult (PND60\u201370) rats. Additionally, the impact of rapamycin pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the brain was assessed in adult rats. Our results show that neonatal ethanol exposure induced deficits in spatial memory and reversal learning in adulthood, but the reversal learning outcome may have been due to spatial learning impairments rather than cognitive flexibility impairments. Furthermore, in adulthood the ethanol treated rats were also more sensitive to the rewarding effect of ethanol than the control group. Rapamycin prevented the neonatal effect of ethanol and normalized the GluN2B down-regulation in the hippocampus and the prefrontal cortex, as well as normalized this subunit\u2019s up-regulation in the striatum of adult rats. Our results suggest that rapamycin and related drugs may hold promise as a preventive therapy for fetal alcohol spectrum disorders.<\/jats:p>","DOI":"10.3390\/biom11050650","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T10:41:58Z","timestamp":1619606518000},"page":"650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["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"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-1968","authenticated-orcid":false,"given":"Malgorzata","family":"Lopatynska-Mazurek","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-8684","authenticated-orcid":false,"given":"Anna","family":"Antolak","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Biochemistry, Faculty of Materials Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 Ave., 30-059 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel","family":"Grochecki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-0633","authenticated-orcid":false,"given":"Ewa","family":"Gibula-Tarlowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0158-8059","authenticated-orcid":false,"given":"Anna","family":"Bodzon-Kulakowska","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Biochemistry, Faculty of Materials Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 Ave., 30-059 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Listos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4511-1241","authenticated-orcid":false,"given":"Piotr","family":"Suder","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Biochemistry, Faculty of Materials Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 Ave., 30-059 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy","family":"Silberring","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Biochemistry, Faculty of Materials Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 Ave., 30-059 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00787-014-0571-6","article-title":"Fetal alcohol spectrum disorders","volume":"23","author":"Freunscht","year":"2014","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_2","first-page":"88","article-title":"Fetal alcohol spectrum disorders: Guidance for recognition, diagnosis, differential diagnosis and referral","volume":"44","author":"Senturias","year":"2014","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0140-6736(73)91092-1","article-title":"Recognition of the fetal alcohol syndrome in early infancy","volume":"3","author":"Jones","year":"1973","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1017\/S1355617708081368","article-title":"Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood","volume":"14","author":"Willoughby","year":"2008","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/17518420902980118","article-title":"A review of the verbal and visual memory impairments in children with foetal alcohol spectrum disorders","volume":"12","author":"Manji","year":"2009","journal-title":"Dev. Neurorehabilit."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/BF03033301","article-title":"The role of signaling molecules in reward-related incentive learning","volume":"6","author":"Beninger","year":"2004","journal-title":"Neurotox. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00213-007-0893-x","article-title":"Conditioned drug reward enhances subsequent spatial learning and memory in rats","volume":"195","author":"Zhai","year":"2007","journal-title":"Psychopharmacology"},{"key":"ref_8","first-page":"4","article-title":"Addiction and cognition","volume":"5","author":"Gould","year":"2010","journal-title":"Addict. Sci. Clin. Pract."},{"key":"ref_9","first-page":"7","article-title":"Memory Systems and the Addicted Brain","volume":"25","author":"Goodman","year":"2016","journal-title":"Front. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3389\/fpsyt.2018.00150","article-title":"Pre-conceptional and Peri-Gestational Maternal Binge Alcohol Drinking Produces Inheritance of Mood Disturbances and Alcohol Vulnerability in the Adolescent Offspring","volume":"23","author":"Brancato","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/01.ALC.0000171046.78556.66","article-title":"Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: A theoretical review","volume":"29","author":"Spear","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.neuropharm.2008.07.030","article-title":"Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure","volume":"55","author":"Barbier","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pnpbp.2018.03.006","article-title":"Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking","volume":"8","author":"Cantacorps","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/adb.12176","article-title":"Moderate alcohol exposure during early brain development increases stimulus-response habits in adulthood","volume":"21","author":"Parker","year":"2016","journal-title":"Addict. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.2174\/092986712799462711","article-title":"The glutamatergic neurotransmission in the central nervous system","volume":"19","author":"Marmiroli","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5751","DOI":"10.1101\/cshperspect.a005751","article-title":"Synapses and memory storage","volume":"4","author":"Mayford","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17641","DOI":"10.1523\/JNEUROSCI.3406-13.2013","article-title":"Drug-evoked synaptic plasticity causing addictive behavior","volume":"33","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pierrefiche, O. (2017). Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life. Brain Sci., 7.","DOI":"10.3390\/brainsci7120157"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.neuroscience.2005.04.010","article-title":"Synergistic effects of the peptide fragment D-NAPVSIPQ on ethanol inhibition of synaptic plasticity and NMDA receptors in rat hippocampus","volume":"134","author":"Zhang","year":"2005","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Subbanna, S., and Basavarajappa, B.S. (2020). Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated \u03b2-Catenin Degradation in Neonatal Mice. Brain Sci., 10.","DOI":"10.3390\/brainsci10050271"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbr.2017.01.033","article-title":"Exercise increases mTOR signaling in brain regions involved in cognition and emotional behavior","volume":"14","author":"Lloyd","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1101\/lm.027664.112","article-title":"A recollection of mTOR signaling in learning and memory","volume":"16","author":"Graber","year":"2013","journal-title":"Learn. Mem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/jnc.12725","article-title":"mTOR complex 1: A key player in neuroadaptations induced by drugs of abuse","volume":"130","author":"Neasta","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.tins.2009.11.003","article-title":"mTOR signaling: At the crossroads of plasticity, memory and disease","volume":"33","author":"Hoeffer","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_26","first-page":"4","article-title":"The pharmacology of mTOR inhibition","volume":"21","author":"Guertin","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.4161\/15548627.2014.981916","article-title":"Autophagy and ethanol neurotoxicity","volume":"10","author":"Luo","year":"2014","journal-title":"Autophagy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.4161\/auto.21376","article-title":"Autophagy is a protective response to ethanol neurotoxicity","volume":"8","author":"Chen","year":"2012","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1523\/JNEUROSCI.1217-12.2013","article-title":"Moderate prenatal alcohol exposure reduces plasticity and alters NMDA receptor subunit composition in the dentate gyrus","volume":"16","author":"Brady","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1530-0277.2009.01096.x","article-title":"Hippocampal N-methyl-D-aspartate receptor subunit expression profiles in a mouse model of prenatal alcohol exposure","volume":"34","author":"Allan","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_31","first-page":"83","article-title":"Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat","volume":"14","author":"Bayer","year":"1993","journal-title":"Neurotoxicology"},{"key":"ref_32","unstructured":"Goodlett, C.R., and Johnson, T.B. (1999). Temporal windows of vulnerability to alcohol during the third trimester equivalent: Why \u201cknowing when\u201d matters. Alcohol and Alcoholism: Effects on Brain and Development, Lawrence Erlbaum Associates."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lopatynska-Mazurek, M., Pankowska, A., Gibula-Tarlowska, E., Pietura, R., and Kotlinska, J.H. (2021). Rapamycin Improves Recognition Memory and Normalizes Amino-Acids and Amines Levels in the Hippocampal Dentate Gyrus in Adult Rats Exposed to Ethanol during the Neonatal Period. Biomolecules, 11.","DOI":"10.3390\/biom11030362"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/FBP.0000000000000557","article-title":"Kissorphin improves spatial memory and cognitive flexibility impairment induced by ethanol treatment in the Barnes maze task in rats","volume":"31","author":"Kotlinska","year":"2020","journal-title":"Behav. Pharmcol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gibula-Tarlowska, E., Wydra, K., and Kotlinska, J.H. (2020). Deleterious Effects of Ethanol, \u0394(9)-Tetrahydrocannabinol (THC), and Their Combination on the Spatial Memory and Cognitive Flexibility in Adolescent and Adult Male Rats in the Barnes Maze Task. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070654"},{"key":"ref_36","first-page":"9","article-title":"ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits, in cognitive flexibility induced by withdrawal from \u2019binge-like\u2019 ethanol exposure in rats","volume":"15","author":"Suder","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s00210-016-1269-8","article-title":"Cholinesterase inhibitors, donepezil and rivastigmine, attenuate spatial memory and cognitive flexibility impairment induced by acute ethanol in the Barnes maze task in rats","volume":"389","author":"Gawel","year":"2016","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_38","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-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.neuropharm.2009.07.022","article-title":"Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus","volume":"57","author":"Uslaner","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1046\/j.1471-4159.2000.0752472.x","article-title":"Transient expression of NMDA receptor subunit NR2B in the developing rat heart","volume":"75","author":"Seeber","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Calabrese, F., Guidotti, G., Molteni, R., Racagni, G., Mancini, M., and Riva, M.A. (2012). Stress-Induced Changes of Hippocampal NMDA Receptors: Modulation by Duloxetine Treatment. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037916"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","article-title":"Measurement of protein using bicinchoninic acid","volume":"150","author":"Smith","year":"1985","journal-title":"Anal. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.alcohol.2019.04.001","article-title":"The kisspeptin derivative kissorphin reduces the acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in rats","volume":"81","author":"Grochecki","year":"2019","journal-title":"Alcohol"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/j.1469-7610.2008.01990.x","article-title":"Executive function deficits in children with fetal alcohol spectrum disorders (FASD) measured using the Cambridge Neuropsychological Tests Automated Battery (CANTAB)","volume":"50","author":"Green","year":"2009","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.neubiorev.2006.09.006","article-title":"Neuroimaging and fetal alcohol spectrum disorders","volume":"31","author":"Spadoni","year":"2007","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bbr.2006.07.012","article-title":"Adult rat\u2019s offspring of alcoholic mothers are impaired on spatial learning and object recognition in the Can test","volume":"174","author":"Guerri","year":"2006","journal-title":"Behav. Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/acer.13598","article-title":"Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice","volume":"42","author":"Xu","year":"2018","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/nlme.1995.0009","article-title":"Sex differences in vulnerability to developmental spatial learning deficits induced by limited binge alcohol exposure in neonatal rats","volume":"64","author":"Goodlett","year":"1995","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1530-0277.2002.tb02435.x","article-title":"Selective and enduring deficits in spatial learning after limited neonatal binge alcohol exposure in male rats","volume":"26","author":"Johnson","year":"2002","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.alcohol.2013.12.001","article-title":"Effects of one- and three-day binge alcohol exposure in neonatal C57BL\/6 mice on spatial learning and memory in adolescence and adulthood","volume":"48","author":"Wagner","year":"2014","journal-title":"Alcohol"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41386-018-0181-y","article-title":"CB1R regulates CDK5 signaling and epigenetically controls Rac1 expression contributing to neurobehavioral abnormalities in mice postnatally exposed to ethanol","volume":"44","author":"Joshi","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.neuroscience.2019.11.045","article-title":"Early Postnatal Ethanol Exposure in Mice Induces Sex-Dependent Memory Impairment and Reduction of Hippocampal NMDA-R2B Expression in Adulthood","volume":"10","author":"Ieraci","year":"2020","journal-title":"Neuroscience"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/acer.12958","article-title":"Neonatal ethanol exposure impairs trace fear conditioning and alters NMDA receptor subunit expression in adult male and female rats","volume":"40","author":"Goodfellow","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neuroscience.2016.03.021","article-title":"The neural basis of reversal learning: An updated perspective","volume":"14","author":"Izquierdo","year":"2017","journal-title":"Neuroscience"},{"key":"ref_55","first-page":"317","article-title":"Neurotoxicity and neurocognitive impairments with alcohol and drug-use disorders: Potential roles in addiction and recovery","volume":"25","author":"Bowden","year":"2001","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/npp.2012.179","article-title":"An evaluation of the evidence that methamphetamine abuse causes cognitive decline in humans","volume":"38","author":"Dean","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/ADM.0000000000000066","article-title":"Cocaine and cognition: A systematic quantitative review","volume":"8","author":"Potvin","year":"2014","journal-title":"J. Addict. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.brainres.2014.10.044","article-title":"Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging","volume":"1628","author":"London","year":"2015","journal-title":"Brain Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neubiorev.2016.07.020","article-title":"Chronic methamphetamine self-administration disrupts cortical control of cognition","volume":"69","author":"Bernheim","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.bbr.2018.07.030","article-title":"Prenatal ethanol exposure increases risk of psychostimulant addiction","volume":"356","author":"Wang","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/01.ALC.0000156115.35817.21","article-title":"Increased preference for ethanol in the infant rat after prenatal ethanol exposure, expressed on intake and taste reactivity tests","volume":"29","author":"Arias","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.bbr.2011.02.033","article-title":"Impact of early life stress on alcohol consumption and on the short- and long-term responses to alcohol in adolescent female rats","volume":"221","author":"Marrocco","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/BF00176849","article-title":"Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference","volume":"94","author":"Carr","year":"1988","journal-title":"Psychopharmacology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1111\/bph.14901","article-title":"Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice","volume":"177","author":"Cantacorps","year":"2020","journal-title":"Br. J. Pharmcol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20093","DOI":"10.1073\/pnas.1005554107","article-title":"Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders","volume":"16","author":"Neasta","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0165-0173(01)00088-1","article-title":"The neuropsychological basis of addictive behaviour","volume":"36","author":"Everitt","year":"2001","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1046\/j.1360-0443.2001.9611038.x","article-title":"Incentive-sensitization and addiction","volume":"96","author":"Robinson","year":"2001","journal-title":"Addiction"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1111\/acer.13103","article-title":"Effect of Alcohol on Encoding and Consolidation of Memory for Alcohol-Related Images","volume":"40","author":"Weafer","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ajog.2006.01.003","article-title":"Prevention of alcohol-induced learning deficits in fetal alcohol syndrome mediated through NMDA and GABA receptors","volume":"194","author":"Toso","year":"2006","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/AOG.0b013e3181cb59da","article-title":"Reversal of alcohol-induced learning deficits in the young adult in a model of fetal alcohol syndrome","volume":"115","author":"Incerti","year":"2010","journal-title":"Obstet. Gynecol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, N., Chen, L., Cheng, N., Zhang, J., Tian, T., and Lu, W. (2014). Active calcium\/calmodulin-dependent protein kinase II (CaMKII) regulates NMDA receptor mediated postischemic long-term potentiation (i-LTP) by promoting the interaction between CaMKII and NMDA receptors in ischemia. Neural Plast., 2014.","DOI":"10.1155\/2014\/827161"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shipton, O.A., and Paulsen, O. (2013). GluN2A and GluN2B subunit-containing NMDA receptors in hippocampal plasticity. Philos. Trans. R. Soc. B Biol. Sci., 369.","DOI":"10.1098\/rstb.2013.0163"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.neuron.2007.05.002","article-title":"A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain","volume":"54","author":"Ge","year":"2007","journal-title":"Neuron"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1002\/hipo.20349","article-title":"Effects of exercise on NMDA receptor subunit contributions to bidirectional synaptic plasticity in the mouse dentate gyrus","volume":"17","author":"Vasuta","year":"2007","journal-title":"Hippocampus"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1126\/science.8091209","article-title":"The basal ganglia and adaptive motor control","volume":"23","author":"Graybiel","year":"1994","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.neuropharm.2010.01.008","article-title":"Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum","volume":"58","author":"Lovinger","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nrn1919","article-title":"The role of the basal ganglia in habit formation","volume":"7","author":"Yin","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1152\/jn.2000.84.3.1422","article-title":"Regional and postnatal heterogeneity of activity-dependent long-term changes in synaptic efficacy in the dorsal striatum","volume":"84","author":"Partridge","year":"2000","journal-title":"J. Neurophysiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1126\/science.1160575","article-title":"Dichotomous dopaminergic control of striatal synaptic plasticity","volume":"321","author":"Shen","year":"2008","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15124","DOI":"10.1523\/JNEUROSCI.2783-12.2012","article-title":"Ethanol-mediated facilitation of AMPA receptor function in the dorsomedial striatum: Implications for alcohol drinking behavior","volume":"24","author":"Wang","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.alcohol.2020.08.002","article-title":"Prenatal alcohol exposure and maternal glutamine supplementation alter the mTOR signaling pathway in ovine fetal cerebellum and skeletal muscle","volume":"89","author":"Sawant","year":"2020","journal-title":"Alcohol"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/acer.14348","article-title":"Chronic Binge Alcohol Exposure During Pregnancy Alters mTOR System in Rat Fetal Hippocampus","volume":"44","author":"Lee","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"51333","DOI":"10.7554\/eLife.51333","article-title":"mTORC1 in the orbitofrontal cortex promotes habitual alcohol seeking","volume":"11","author":"Morisot","year":"2019","journal-title":"eLife"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/5\/650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:54:41Z","timestamp":1760162081000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/5\/650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,28]]},"references-count":83,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["biom11050650"],"URL":"https:\/\/doi.org\/10.3390\/biom11050650","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,28]]}}}