PMID- 37889278 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20240109 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 241 IP - 1 DP - 2024 Jan TI - Improving behavioral deficits induced by perinatal ethanol and stress exposure in adolescent male rat progeny via maternal melatonin treatment. PG - 153-169 LID - 10.1007/s00213-023-06470-z [doi] AB - BACKGROUND AND AIM: Early-life stressful situations and binge drinking have been thus far acknowledged as two burdensome conditions that potentially give rise to negative outcomes and then synergistically affect brain development. In this context, the hippocampus, with the greatest number of glucocorticoid receptors (GCRs) in the brain, is responsible for regulating negative responses to stress. Prolonged glucocorticoid (GC) exposure can accordingly cause oxidative stress (OS), leading to cognitive and emotional dysfunction. Against this background, melatonin, as a powerful antioxidant and hypothalamus-pituitary-adrenal (HPA) axis regulator, was administered in this study to ameliorate cognitive impairments induced by perinatal ethanol and stress exposure in adolescent male rat progeny. METHODS: Wistar rat dams were exposed to ethanol (4 g/kg) and melatonin (10 mg/kg) from gestational day (GD) 6 to postnatal day (PND) 14 and then limited nesting material (LNS) from PND0 to PND14 individually or in combination. Maternal behavior was then investigated in mothers. Afterward, the plasma corticosterone (CORT) concentration, the OS marker, the corticotropin-releasing hormone receptor type 1 (CRHR1) expression, and the GCR and brain-derived neurotrophic factor (BDNF) levels were measured in the male pups. Moreover, behavioral tasks, including the elevated plus maze (EPM), the Morris water maze (MWM), the novel object recognition (NORT), and the object-location memory (OLM) tests were completed and assessed. RESULTS: The quantity and quality of maternal care significantly decreased in the mothers with dual exposure to ethanol and stress. The plasma CORT concentration in the progeny also dropped in the Ethanol + LNS group, but the risk-taking behavior elevated significantly. The ethanol and stress exposure further revealed a significant fall in the GCR and CRHR1 expression levels, compared with stress alone. The results of learning and memory tasks also indicated a significant reduction in spatial learning and memory among animals exposed to ethanol and stress. The BDNF mRNA levels correspondingly increased in the Ethanol + LNS group, compared with LNS alone. In the presence of ethanol and stress, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities correspondingly declined. On the other hand, the malondialdehyde (MDA) levels augmented in the hippocampus of the animals with ethanol and LNS dual exposure, as compared with the control group. Melatonin treatment (MT) thus improved nursing behaviors in dams, prevented OS, enhanced the CRHR1 and GCR expression, and reduced the BDNF levels to the similar ones in the control group. The animals in the Ethanol + LNS + MT group ultimately showed an ameliorated performance at behavioral tasks, including the memory and risk-taking behavior. CONCLUSION: It was concluded that MT could prevent stress response and memory impairments arising from dual exposure to ethanol and stress by inhibiting OS. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Bagheri, Farzaneh AU - Bagheri F AD - School of Biology, Damghan University, Damghan, Iran. FAU - Goudarzi, Iran AU - Goudarzi I AD - School of Biology, Damghan University, Damghan, Iran. irangoudarzi@du.ac.ir. FAU - Lashkarbolouki, Taghi AU - Lashkarbolouki T AD - School of Biology, Damghan University, Damghan, Iran. FAU - Elahdadi Salmani, Mahmoud AU - Elahdadi Salmani M AD - School of Biology, Damghan University, Damghan, Iran. FAU - Goudarzi, Afsaneh AU - Goudarzi A AD - Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Morley-Fletcher, Sara AU - Morley-Fletcher S AD - Univ. Lille, CNRS, UMR 8576 - UGSF - Unite de Glycobiologie Structurale Et Fonctionnelle, 59000, Lille, France. LA - eng PT - Journal Article DEP - 20231027 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - JL5DK93RCL (Melatonin) RN - 3K9958V90M (Ethanol) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Antioxidants) SB - IM MH - Pregnancy MH - Female MH - Rats MH - Animals MH - Male MH - *Melatonin/pharmacology/metabolism MH - Rats, Wistar MH - Ethanol/toxicity MH - Brain-Derived Neurotrophic Factor/metabolism MH - Antioxidants/metabolism MH - Spatial Learning MH - Hippocampus/metabolism MH - Maze Learning OTO - NOTNLM OT - Early-life stress OT - Ethanol OT - Learning and memory OT - Melatonin OT - Oxidative stress OT - Rat pups OT - Risk-taking behavior EDAT- 2023/10/27 12:42 MHDA- 2024/01/09 06:42 CRDT- 2023/10/27 11:04 PHST- 2023/02/10 00:00 [received] PHST- 2023/09/25 00:00 [accepted] PHST- 2024/01/09 06:42 [medline] PHST- 2023/10/27 12:42 [pubmed] PHST- 2023/10/27 11:04 [entrez] AID - 10.1007/s00213-023-06470-z [pii] AID - 10.1007/s00213-023-06470-z [doi] PST - ppublish SO - Psychopharmacology (Berl). 2024 Jan;241(1):153-169. doi: 10.1007/s00213-023-06470-z. Epub 2023 Oct 27.