Maternal Separation Alters Ethanol Drinking and Reversal Learning Processes in Adolescent Rats: The Impact of Sex and Glycine Transporter Type 1 (GlyT1) Inhibitor

被引:9
作者
Filarowska-Jurko, Joanna [1 ]
Komsta, Lukasz [2 ]
Smaga, Irena [3 ]
Surowka, Paulina [3 ]
Marszalek-Grabska, Marta [4 ]
Grochecki, Pawel [1 ]
Nizio, Dorota [5 ]
Filip, Malgorzata [3 ]
Kotlinska, Jolanta H. [1 ]
机构
[1] Med Univ, Dept Pharmacol & Pharmacodynam, Chodzki 4A, PL-20093 Lublin, Poland
[2] Med Univ, Dept Med Chem, Jaczewskiego 4, PL-20090 Lublin, Poland
[3] Polish Acad Sci, Maj Inst Pharmacol, Dept Drug Addict Pharmacol, Smetna 12, PL-31324 Krakow, Poland
[4] Med Univ, Dept Expt & Clin Pharmacol, Jaczewskiego 8b, PL-20090 Lublin, Poland
[5] Med Univ, Expt Med Ctr, Jaczewskiego 8, PL-20090 Lublin, Poland
关键词
maternal separation; male; female; ethanol drinking; reversal learning; NMDA receptor subunits; GlyT1; inhibitor; LONG-TERM POTENTIATION; NMDA RECEPTOR; PREFRONTAL CORTEX; D-SERINE; ALCOHOL-DRINKING; SPATIAL MEMORY; D-CYCLOSERINE; WISTAR RATS; EXPRESSION; MODEL;
D O I
10.3390/ijms23105350
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:21
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