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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Published in:	International journal of molecular sciences Vol. 23; no. 10; p. 5350
Main Authors:	Filarowska-Jurko, Joanna, Komsta, Lukasz, Smaga, Irena, Surowka, Paulina, Marszalek-Grabska, Marta, Grochecki, Pawel, Nizio, Dorota, Filip, Malgorzata, Kotlinska, Jolanta H
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 11-05-2022 MDPI
Subjects:	Adults Alcohol Alcohol abuse Alcohol Drinking Animal models Animals Binding sites Choice learning Drinking Drinking behavior Drug abuse Ethanol Ethanol - pharmacology ethanol drinking Female Females Glutamate receptors Glycine Glycine - pharmacology Glycine Plasma Membrane Transport Proteins Glycine transporter GlyT1 inhibitor Inhibitors Male male/female Males Maternal Deprivation maternal separation Maze learning N-Methyl-D-aspartic acid receptors Neostriatum NMDA receptor subunits Prefrontal cortex Rats Reversal Learning Rodents Separation male/female maternal separation reversal learning NMDA receptor subunits GlyT1 inhibitor ethanol drinking
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Summary:	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 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms23105350