Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor
Adverse early life experiences are associated with an enhanced risk for mental and physical health problems, including substance abuse. Despite clinical evidence, the mechanisms underlying these relationships are not fully understood. Maternal separation (MS) is a commonly used animal model of early...
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5350 |
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| author | Joanna Filarowska-Jurko Lukasz Komsta Irena Smaga Paulina Surowka Marta Marszalek-Grabska Pawel Grochecki Dorota Nizio Malgorzata Filip Jolanta H. Kotlinska |
| author_facet | Joanna Filarowska-Jurko Lukasz Komsta Irena Smaga Paulina Surowka Marta Marszalek-Grabska Pawel Grochecki Dorota Nizio Malgorzata Filip Jolanta H. Kotlinska |
| author_sort | Joanna Filarowska-Jurko |
| collection | DOAJ |
| description | Adverse early life experiences are associated with an enhanced risk for mental and physical health problems, including substance abuse. Despite clinical evidence, the mechanisms underlying these relationships are not fully understood. Maternal separation (MS) is a commonly used animal model of early neglect. The aim of the current study is to determine whether the N-methyl-D-aspartate receptor (NMDAR)/glycine sites are involved in vulnerability to alcohol consumption (two-bottle choice paradigm) and reversal learning deficits (Barnes maze task) in adolescent rats subjected to the MS procedure and whether these effects are sex dependent. By using ELISA, we evaluated MS-induced changes in the NMDAR subunits (GluN1, GluN2A, GluN2B) expression, especially in the glycine-binding subunit, GluN1, in the prefrontal cortex (PFC) and ventral striatum (vSTR) of male/female rats. Next, we investigated whether Org 24598, a glycine transporter 1 (GlyT1) inhibitor, was able to modify ethanol drinking in adolescent and adult male/female rats with prior MS experience and reversal learning in the Barnes maze task. Our findings revealed that adolescent MS female rats consumed more alcohol which may be associated with a substantial increase in GluN1 subunit of NMDAR in the PFC and vSTR. Org 24598 decreased ethanol intake in both sexes with a more pronounced decrease in ethanol consumption in adolescent female rats. Furthermore, MS showed deficits in reversal learning in both sexes<b>.</b> Org 24598 ameliorated reversal learning deficits, and this effect was reversed by the NMDAR/glycine site inhibitor, L-701,324. Collectively, our results suggest that NMDAR/glycine sites might be targeted in the treatment of alcohol abuse in adolescents with early MS, especially females. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:45:24Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6cd393eb0bf24f3e94968c747a4ab8222023-11-23T11:21:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310535010.3390/ijms23105350Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) InhibitorJoanna Filarowska-Jurko0Lukasz Komsta1Irena Smaga2Paulina Surowka3Marta Marszalek-Grabska4Pawel Grochecki5Dorota Nizio6Malgorzata Filip7Jolanta H. Kotlinska8Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, PolandDepartment of Medicinal Chemistry, Medical University, Jaczewskiego 4, 20-090 Lublin, PolandDepartment of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-324 Krakow, PolandDepartment of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-324 Krakow, PolandDepartment of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8b, 20-090 Lublin, PolandDepartment of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, PolandExperimental Medicine Center, Medical University, Jaczewskiego 8, 20-090 Lublin, PolandDepartment of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-324 Krakow, PolandDepartment of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, PolandAdverse early life experiences are associated with an enhanced risk for mental and physical health problems, including substance abuse. Despite clinical evidence, the mechanisms underlying these relationships are not fully understood. Maternal separation (MS) is a commonly used animal model of early neglect. The aim of the current study is to determine whether the N-methyl-D-aspartate receptor (NMDAR)/glycine sites are involved in vulnerability to alcohol consumption (two-bottle choice paradigm) and reversal learning deficits (Barnes maze task) in adolescent rats subjected to the MS procedure and whether these effects are sex dependent. By using ELISA, we evaluated MS-induced changes in the NMDAR subunits (GluN1, GluN2A, GluN2B) expression, especially in the glycine-binding subunit, GluN1, in the prefrontal cortex (PFC) and ventral striatum (vSTR) of male/female rats. Next, we investigated whether Org 24598, a glycine transporter 1 (GlyT1) inhibitor, was able to modify ethanol drinking in adolescent and adult male/female rats with prior MS experience and reversal learning in the Barnes maze task. Our findings revealed that adolescent MS female rats consumed more alcohol which may be associated with a substantial increase in GluN1 subunit of NMDAR in the PFC and vSTR. Org 24598 decreased ethanol intake in both sexes with a more pronounced decrease in ethanol consumption in adolescent female rats. Furthermore, MS showed deficits in reversal learning in both sexes<b>.</b> Org 24598 ameliorated reversal learning deficits, and this effect was reversed by the NMDAR/glycine site inhibitor, L-701,324. Collectively, our results suggest that NMDAR/glycine sites might be targeted in the treatment of alcohol abuse in adolescents with early MS, especially females.https://www.mdpi.com/1422-0067/23/10/5350maternal separationmale/femaleethanol drinkingreversal learningNMDA receptor subunitsGlyT1 inhibitor |
| spellingShingle | Joanna Filarowska-Jurko Lukasz Komsta Irena Smaga Paulina Surowka Marta Marszalek-Grabska Pawel Grochecki Dorota Nizio Malgorzata Filip Jolanta H. Kotlinska Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor International Journal of Molecular Sciences maternal separation male/female ethanol drinking reversal learning NMDA receptor subunits GlyT1 inhibitor |
| title | Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor |
| title_full | Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor |
| title_fullStr | Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor |
| title_full_unstemmed | Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor |
| title_short | Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor |
| title_sort | maternal separation alters ethanol drinking and reversal learning processes in adolescent rats the impact of sex and glycine transporter type 1 glyt1 inhibitor |
| topic | maternal separation male/female ethanol drinking reversal learning NMDA receptor subunits GlyT1 inhibitor |
| url | https://www.mdpi.com/1422-0067/23/10/5350 |
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