{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T02:56:06Z","timestamp":1768359366509,"version":"3.49.0"},"reference-count":101,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Statutory Funds of the Medical University of Lublin","award":["DS 22\/2020"],"award-info":[{"award-number":["DS 22\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The mammalian target of rapamycin (mTOR), a serine\/ threonine kinase, is implicated in synaptic plasticity by controlling protein synthesis. Research suggests that ethanol exposure during pregnancy alters the mTOR signaling pathway in the fetal hippocampus. Thus, we investigated the influence of pre-treatment with rapamycin, an mTORC1 inhibitor, on the development of recognition memory deficits in adult rats that were neonatally exposed to ethanol. In the study, male and female rat pups received ethanol (5 g\/kg\/day) by intragastric intubation at postanatal day (PND 4-9), an equivalent to the third trimester of human pregnancy. Rapamycin (3 and 10 mg\/kg) was given intraperitoneally before every ethanol administration. Short- and long-term recognition memory was assessed in the novel object recognition (NOR) task in adult (PND 59\/60) rats. Locomotor activity and anxiety-like behavior were also evaluated to exclude the influence of such behavior on the outcome of the memory task. Moreover, the effects of rapamycin pre-treatment during neonatal ethanol exposure on the content of amino-acids and amines essential for the proper development of cognitive function in the dentate gyrus (DG) of the hippocampus was evaluated using proton magnetic resonance spectroscopy (1H MRS) in male adult (PND 60) rats. Our results show the deleterious effect of ethanol given to neonatal rats on long-term recognition memory in adults. The effect was more pronounced in male rather than female rats. Rapamycin reversed this ethanol-induced memory impairment and normalized the levels of amino acids and amines in the DG. This suggests the involvement of mTORC1 in the deleterious effect of ethanol on the developing brain.<\/jats:p>","DOI":"10.3390\/biom11030362","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T20:55:44Z","timestamp":1614459344000},"page":"362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["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"],"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, Lublin, 20-059 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-1244","authenticated-orcid":false,"given":"Anna","family":"Pankowska","sequence":"additional","affiliation":[{"name":"Department of Radiography, Medical University, Lublin, 20-081 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, Lublin, 20-059 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radoslaw","family":"Pietura","sequence":"additional","affiliation":[{"name":"Department of Radiography, Medical University, Lublin, 20-081 Lublin, 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, Lublin, 20-059 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1530-0277.2012.01955.x","article-title":"Determining the threshold for alcohol-induced brain damage: New evidence with gliosis markers","volume":"37","author":"Hayes","year":"2013","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11065-011-9166-x","article-title":"Fetal alcohol spectrum disorders: An overview","volume":"21","author":"Riley","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11065-011-9167-9","article-title":"Fetal alcohol spectrum disorders: Neuropsychological and behavioral features","volume":"21","author":"Mattson","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/15353702-0323006-03","article-title":"Fetal alcohol spectrum disorders: An overview with emphasis on changes in brain and behavior","volume":"230","author":"Riley","year":"2005","journal-title":"Exp. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/ddrr.72","article-title":"Neuroimaging and fetal alcohol spectrum disorders","volume":"15","author":"Norman","year":"2009","journal-title":"Dev. Disabil. Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.brainresrev.2010.04.011","article-title":"Hippocampal cell loss and neurogenesis after fetal alcohol exposure: Insights from different rodent models","volume":"64","author":"Boehme","year":"2010","journal-title":"Brain Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s10597-017-0104-0","article-title":"Fetal Alcohol Spectrum Disorders: Characteristics, Complications, and Treatment","volume":"53","author":"Wilhoit","year":"2017","journal-title":"Community Ment. Health J."},{"key":"ref_8","first-page":"168","article-title":"Drinking patterns and alcohol-related birth defects","volume":"25","author":"Maier","year":"2001","journal-title":"Alcohol. Res. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0006-8993(91)90973-Y","article-title":"The effects of chronic ethanol exposure on N-methyl-D-aspartate-stimulated overflow of [3H] catecholamines from rat brain","volume":"547","author":"Brown","year":"1991","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1076\/chin.9.2.117.14503","article-title":"Neurocognitive impairment in early adolescence following prenatal alcohol exposure of varying duration","volume":"9","author":"Korkman","year":"2003","journal-title":"Child Neuropsychol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/j.1530-0277.1995.tb01024.x","article-title":"Specific impairments in self-regulation in children exposed to alcohol prenatally","volume":"19","author":"Kodituwakku","year":"1995","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/1044-7431(90)90022-V","article-title":"Effect of prenatal exposure to ethanol on the activity of the hypothalamic-pituitary-adrenal axis of the offspring: Importance of the time of exposure to ethanol and possible modulating mechanisms","volume":"1","author":"Lee","year":"1990","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1523\/JNEUROSCI.09-01-00216.1989","article-title":"Topographical organization of the entorhinal projection to the dentate gyrus of the monkey","volume":"9","author":"Witter","year":"1989","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/cne.903070308","article-title":"Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex","volume":"307","author":"Witter","year":"1991","journal-title":"J. Comp. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1101\/lm.1172609","article-title":"Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats","volume":"16","author":"Jessberger","year":"2009","journal-title":"Learn Mem."},{"key":"ref_16","first-page":"1815371","article-title":"Novelty and novel objects increase c-Fos immunoreactivity in mossy cells in the mouse dentate gyrus","volume":"27","author":"Bernstein","year":"2019","journal-title":"Neural Plast."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14069","DOI":"10.1038\/s41598-017-13853-8","article-title":"The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory","volume":"7","author":"Dillon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1098\/rstb.1971.0078","article-title":"Simple memory: A theory for archicortex","volume":"262","author":"Marr","year":"1971","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0166-4328(88)90157-X","article-title":"A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data","volume":"31","author":"Ennaceur","year":"1988","journal-title":"Behav. Brain Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.conb.2006.10.009","article-title":"Intermediate-term processes in memory formation","volume":"16","author":"Stough","year":"2006","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.bbr.2008.12.034","article-title":"Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition","volume":"200","author":"Taglialatela","year":"2009","journal-title":"Behav. Brain. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"a021741","DOI":"10.1101\/cshperspect.a021741","article-title":"The regulation of transcription in memory consolidation","volume":"7","author":"Alberini","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1177\/1073858414547934","article-title":"Neural Plasticity and Memory: Is Memory Encoded in Hydrogen Bonding Patterns?","volume":"22","author":"Amtul","year":"2016","journal-title":"Neuroscientist."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1126\/sageke.2004.36.pe34","article-title":"TOR pathway: Linking nutrient sensing to life span","volume":"2004","author":"Kapahi","year":"2004","journal-title":"Sci. Aging Knowl. Environ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ceb.2005.02.008","article-title":"The expanding TOR signaling network","volume":"17","author":"Martin","year":"2005","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"24553","DOI":"10.1074\/jbc.M110.202341","article-title":"mTORC2 protein complex-mediated Akt (Protein Kinase B) Serine 473 Phosphorylation is not required for Akt1 activity in human platelets","volume":"286","author":"Moore","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1385\/MN:34:3:205","article-title":"The growing role of mTOR in neuronal development and plasticity","volume":"34","author":"Jaworski","year":"2006","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuron.2008.10.055","article-title":"Translational control of long-lasting synaptic plasticity and memory","volume":"61","author":"Sossin","year":"2009","journal-title":"Neuron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1126\/science.1142365","article-title":"Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area","volume":"317","author":"Mameli","year":"2007","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.nlm.2007.12.004","article-title":"Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation","volume":"90","author":"Blundell","year":"2008","journal-title":"Neurobiol. Learn Mem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/nn.2369","article-title":"Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling","volume":"12","author":"Puighermanal","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1073\/pnas.012605299","article-title":"A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus","volume":"99","author":"Tang","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","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_34","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":"107","author":"Neasta","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.reprotox.2018.01.004","article-title":"Fetal regional brain protein signature in FASD rat model","volume":"76","author":"Wesseling","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species","volume":"106","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bgm.2014.01.002","article-title":"Biomarkers in fetal alcohol syndrome","volume":"6","author":"Chabenne","year":"2014","journal-title":"Biomark. Genom. Med."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.alcohol.2016.09.027","article-title":"Recognition memory is selectively impaired in adult rats exposed to binge-like doses of ethanol during early postnatal life","volume":"57","author":"MacIlvane","year":"2016","journal-title":"Alcohol"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.alcohol.2012.12.013","article-title":"Effects of early postnatal alcohol exposure on the developing retinogeniculate projections in C57BL\/6 mice","volume":"47","author":"Dursun","year":"2013","journal-title":"Alcohol"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1017\/S1461145713001156","article-title":"Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats","volume":"17","author":"Lin","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s12640-017-9857-z","article-title":"Effects of the Positive Allosteric Modulator of Metabotropic Glutamate Receptor 5, VU-29, on Impairment of Novel Object Recognition Induced by Acute Ethanol and Ethanol Withdrawal in Rats","volume":"33","author":"Suder","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.brainres.2016.04.026","article-title":"Memantine improves memory impairment and depressive-like behavior induced by amphetamine withdrawal in rats","volume":"1642","author":"Jenda","year":"2016","journal-title":"Brain Res."},{"key":"ref_45","first-page":"55718","article-title":"Novel Object Recognition Test for the Investigation of Learning and Memory in Mice","volume":"126","author":"Lueptow","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.nlm.2004.03.005","article-title":"On the delay-dependent involvement of the hippocampus in object recognition memory","volume":"82","author":"Hammond","year":"2004","journal-title":"Neurobiol. Learn Mem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.pnpbp.2013.04.013","article-title":"The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats","volume":"45","author":"Koltunowska","year":"2013","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.yhbeh.2013.01.007","article-title":"Alcohol administration blocks stress-induced impairments in memory and anxiety and alters hippocampal neurotransmitter receptor expression in male rats","volume":"63","author":"Gomez","year":"2013","journal-title":"Horm. Behav."},{"key":"ref_49","first-page":"1998","article-title":"Neuropsychological deficits in adolescents with fetal alcohol syndrome: Clinical findings","volume":"22","author":"Olson","year":"1998","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1530-0277.2010.01323.x","article-title":"The effects of maternal binge drinking during pregnancy on neural correlates of response inhibition and memory in childhood","volume":"35","author":"Burden","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijdevneu.2008.12.009","article-title":"Effects of neonatal and peripubertal ethanol treatment on various aspects of adult rat behavior and brain anatomy","volume":"27","author":"Koch","year":"2009","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1037\/0735-7044.111.5.985","article-title":"Object-recognition and spatial learning and memory in rats prenatally exposed to ethanol","volume":"111","author":"Kim","year":"1997","journal-title":"Behav. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bbr.2007.08.011","article-title":"Dietary zinc supplementation during pregnancy prevents spatial and object recognition memory impairments caused by early prenatal ethanol exposure","volume":"186","author":"Summers","year":"2008","journal-title":"Behav. Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1111\/j.1530-0277.2011.01549.x","article-title":"Local and regional network function in behaviorally relevant cortical circuits of adult mice following postnatal alcohol exposure","volume":"35","author":"Wilson","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"20150123","DOI":"10.1098\/rstb.2015.0123","article-title":"An examination of sex differences in the effects of early-life opiate and alcohol exposure","volume":"371","author":"Terasaki","year":"2016","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1093\/alcalc\/agp061","article-title":"Sexually dimorphic effects of alcohol exposure during development on the processing of social cues","volume":"44","author":"Kelly","year":"2009","journal-title":"Alcohol Alcohol."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.cub.2013.07.002","article-title":"The rodent hippocampus is essential for nonspatial object memory","volume":"23","author":"Cohen","year":"2013","journal-title":"Curr. Biol."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0892-0362(97)00062-7","article-title":"Neonatal binge ethanol exposure using intubation: Timing and dose effects on place learning","volume":"19","author":"Goodlett","year":"1997","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/j.1530-0277.2001.tb02274.x","article-title":"Alcohol exposure during the brain growth spurt promotes hippocampal seizures, rapid kindling, and spreading depression","volume":"25","author":"Bonthius","year":"2001","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/syn.20711","article-title":"Postnatal binge-like alcohol exposure decreases dendritic complexity while increasing the density of mature spines in mPFC Layer II\/III pyramidal neurons","volume":"64","author":"Hamilton","year":"2010","journal-title":"Synapse"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1111\/j.1530-0277.2007.00528.x","article-title":"Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure","volume":"31","author":"Klintsova","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.alcohol.2010.03.001","article-title":"Repeated third trimester-equivalent ethanol exposure inhibits long-term potentiation in the hippocampal CA1 region of neonatal rats","volume":"44","author":"Puglia","year":"2010","journal-title":"Alcohol"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/cne.901900107","article-title":"Development of the hippocampal region in the rat I. Neurogenesis examined with 3H-thymidine autoradiography","volume":"190","author":"Bayer","year":"1980","journal-title":"J. Comp. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF00238626","article-title":"Changes in the total number of dentate granule cells in juvenile and adult rats: A correlated volumetric and 3 H-thymidine autoradiographic study","volume":"46","author":"Bayer","year":"1982","journal-title":"Exp. Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/(SICI)1098-1063(1999)9:5<562::AID-HIPO10>3.0.CO;2-X","article-title":"Hippocampal formation lesions produce memory impairment in the rhesus monkey","volume":"9","author":"Rosene","year":"1999","journal-title":"Hippocampus"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/hipo.450010323","article-title":"Equivalent impairment of spatial and nonspatial memory following damage to the human hippocampus","volume":"1","author":"Cave","year":"1991","journal-title":"Hippocampus"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1037\/0735-7044.111.4.667","article-title":"Impaired recognition memory in patients with lesions limited to the hippocampal formation","volume":"111","author":"Reed","year":"1997","journal-title":"Behav. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1523\/JNEUROSCI.20-01-00451.2000","article-title":"Impaired recognition memory in monkeys after damage limited to the hippocampal region","volume":"20","author":"Zola","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8853","DOI":"10.1523\/JNEUROSCI.20-23-08853.2000","article-title":"Impaired recognition memory in rats after damage to the hippocampus","volume":"20","author":"Clark","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1111\/acer.14170","article-title":"Impaired Bidirectional Synaptic Plasticity in Juvenile Offspring Following Prenatal Ethanol Exposure","volume":"43","author":"Fontaine","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/hipo.22414","article-title":"Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat hippocampus","volume":"25","author":"Kervern","year":"2015","journal-title":"Hippocampus"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bbapap.2009.12.001","article-title":"Dissecting the role of mTOR: Lessons from mTOR inhibitors","volume":"1804","author":"Dowling","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/S0753-3322(02)00285-8","article-title":"Glutamine and glutamate","volume":"56","author":"Tapiero","year":"2002","journal-title":"Biomed. Pharmacother."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Waagepetersen, H.S., Sonnewald, U., and Schousboe, A. (2007). Glutamine, Glutamate, and GABA: Metabolic aspects. Handbook of Neurochemistry and Molecular Neurobiology: Amino Acids and Peptides in the Nervous System, Springer.","DOI":"10.1007\/978-0-387-30373-4_1"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pneurobio.2018.10.001","article-title":"Role of glutamatergic system and mesocorticolimbic circuits in alcohol dependence","volume":"171","author":"Alasmari","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1067\/mpd.2001.110979","article-title":"Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: The role of child abuse","volume":"138","author":"Ruppel","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1203\/00006450-199112000-00021","article-title":"Hypoxia-ischemia stimulates hippocampal glutamate efflux in perinatal rat brain: An in vivo microdialysis study","volume":"30","author":"Silverstein","year":"1991","journal-title":"Pediatric Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/0091-3057(90)90383-S","article-title":"Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxytryptamine synthesis in rats: A possible mechanism by which stress influences brain development","volume":"35","author":"Peters","year":"1990","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.expneurol.2004.03.027","article-title":"Development of neurotransmitter systems during critical periods","volume":"190","author":"Herlenius","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1369-1600.2010.00272.x","article-title":"Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release","volume":"16","author":"Chefer","year":"2011","journal-title":"Addict. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.biopsych.2010.03.003","article-title":"Are metabotropic glutamate receptors promising targets for the treatment of alcoholism?","volume":"67","author":"Spanagel","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.283.5398.70","article-title":"Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain","volume":"283","author":"Ikonomidou","year":"1999","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.nbd.2004.08.006","article-title":"Apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning\/memory deficits in juveniles followed by progressive functional recovery in adults","volume":"17","author":"Wozniak","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1113\/jphysiol.1983.sp014478","article-title":"Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus","volume":"334","author":"Collingridge","year":"1983","journal-title":"J. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1101\/lm.46102","article-title":"Effects of stress and hippocampal NMDA receptor antagonism on recognition memory in rats","volume":"9","author":"Baker","year":"2002","journal-title":"Learn Mem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/43432","article-title":"Genetic enhancement of learning and memory in mice","volume":"401","author":"Tang","year":"1999","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jpeds.2006.06.065","article-title":"The fetal origins of memory: The role of dietary choline in optimal brain development","volume":"149","author":"Zeisel","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/(SICI)1098-1063(2000)10:1<94::AID-HIPO11>3.0.CO;2-T","article-title":"Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy","volume":"10","author":"Berman","year":"2000","journal-title":"Hippocampus"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bbr.2012.10.016","article-title":"Decreased acetylcholine release delays the consolidation of object recognition memory","volume":"238","author":"Cammarota","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.alcohol.2017.07.010","article-title":"Regional dysregulation of taurine and related amino acids in the fetal rat brain following gestational alcohol exposure","volume":"66","author":"Naik","year":"2018","journal-title":"Alcohol"},{"key":"ref_94","first-page":"217","article-title":"Functional morphological and spectroscopic measurements of the hippocampus in fetal alcohol syndrome","volume":"27","author":"Hamilton","year":"2003","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1111\/j.1530-0277.2008.00747.x","article-title":"Neonatal alcohol-induced region-dependent changes in rat brain neurochemistry measured by high-resolution magnetic resonance spectroscopy","volume":"32","author":"McMechan","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.neuint.2013.02.007","article-title":"Quantitative assessment of neurochemical changes in a rat model of long-term alcohol consumption as detected by in vivo and ex vivo proton nuclear magnetic resonance spectroscopy","volume":"62","author":"Lee","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: One drug, many effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab."},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/acel.12194","article-title":"Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction","volume":"13","author":"Miller","year":"2014","journal-title":"Aging Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fnmol.2014.00083","article-title":"Divergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice","volume":"7","author":"Rodriguez","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1016\/j.chest.2020.08.1573","article-title":"Effect of gender on the treatment responses to rapamycin on the progression of emphysema in cigarette smoke-exposed mice","volume":"158","author":"Earasi","year":"2020","journal-title":"Chest"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/362\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:29:51Z","timestamp":1760160591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/3\/362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,27]]},"references-count":101,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["biom11030362"],"URL":"https:\/\/doi.org\/10.3390\/biom11030362","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,27]]}}}