PMID- 33924998
OWN - NLM
STAT- MEDLINE
DCOM- 20210922
LR  - 20210922
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 11
IP  - 5
DP  - 2021 Apr 28
TI  - Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction 
      and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats 
      Exposed to Ethanol during the Neonatal Period.
LID - 10.3390/biom11050650 [doi]
LID - 650
AB  - Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) 
      signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol 
      during the neonatal period, we investigated the influence of rapamycin, an mTOR 
      Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning 
      in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 
      1.5 g/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 
      and 10 mg/kg) was given before intragastric ethanol (5 g/kg/day) administration 
      at postnatal day (PND)4-9 (an equivalent to the third trimester of human 
      pregnancy). Spatial memory/reversal learning and rewarding ethanol effect were 
      evaluated in adult (PND60-70) rats. Additionally, the impact of rapamycin 
      pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the 
      brain was assessed in adult rats. Our results show that neonatal ethanol exposure 
      induced deficits in spatial memory and reversal learning in adulthood, but the 
      reversal learning outcome may have been due to spatial learning impairments 
      rather than cognitive flexibility impairments. Furthermore, in adulthood the 
      ethanol treated rats were also more sensitive to the rewarding effect of ethanol 
      than the control group. Rapamycin prevented the neonatal effect of ethanol and 
      normalized the GluN2B down-regulation in the hippocampus and the prefrontal 
      cortex, as well as normalized this subunit's up-regulation in the striatum of 
      adult rats. Our results suggest that rapamycin and related drugs may hold promise 
      as a preventive therapy for fetal alcohol spectrum disorders.
FAU - Lopatynska-Mazurek, Malgorzata
AU  - Lopatynska-Mazurek M
AUID- ORCID: 0000-0001-5266-1968
AD  - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 
      20-093 Lublin, Poland.
FAU - Antolak, Anna
AU  - Antolak A
AUID- ORCID: 0000-0002-8008-8684
AD  - Department of Analytical Chemistry and Biochemistry, Faculty of Materials 
      Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 
      Ave., 30-059 Krakow, Poland.
FAU - Grochecki, Pawel
AU  - Grochecki P
AD  - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 
      20-093 Lublin, Poland.
FAU - Gibula-Tarlowska, Ewa
AU  - Gibula-Tarlowska E
AUID- ORCID: 0000-0001-7791-0633
AD  - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 
      20-093 Lublin, Poland.
FAU - Bodzon-Kulakowska, Anna
AU  - Bodzon-Kulakowska A
AUID- ORCID: 0000-0002-0158-8059
AD  - Department of Analytical Chemistry and Biochemistry, Faculty of Materials 
      Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 
      Ave., 30-059 Krakow, Poland.
FAU - Listos, Joanna
AU  - Listos J
AD  - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 
      20-093 Lublin, Poland.
FAU - Kedzierska, Ewa
AU  - Kedzierska E
AD  - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 
      20-093 Lublin, Poland.
FAU - Suder, Piotr
AU  - Suder P
AUID- ORCID: 0000-0003-4511-1241
AD  - Department of Analytical Chemistry and Biochemistry, Faculty of Materials 
      Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 
      Ave., 30-059 Krakow, Poland.
FAU - Silberring, Jerzy
AU  - Silberring J
AD  - Department of Analytical Chemistry and Biochemistry, Faculty of Materials 
      Sciences and Ceramics, AGH University of Science and Technology, Mickiewicza 30 
      Ave., 30-059 Krakow, Poland.
FAU - Kotlinska, Jolanta H
AU  - Kotlinska JH
AUID- ORCID: 0000-0002-4178-1515
AD  - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 
      20-093 Lublin, Poland.
LA  - eng
GR  - DS 22/2020/Medical University of Lublin/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210428
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3K9958V90M (Ethanol)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Alcoholism/metabolism
MH  - Animals
MH  - Animals, Newborn/metabolism
MH  - Brain/drug effects
MH  - Ethanol/*toxicity
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/drug therapy
MH  - Hippocampus/drug effects
MH  - Male
MH  - Prefrontal Cortex/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/metabolism/*pharmacology
MH  - Spatial Learning/*drug effects/physiology
PMC - PMC8147055
OTO - NOTNLM
OT  - adult rats 5
OT  - neonatal ethanol exposure 4
OT  - rapamycin 1
OT  - reward 3
OT  - spatial learning 2
COIS- The authors declare no conflict of interest.
EDAT- 2021/05/01 06:00
MHDA- 2021/09/23 06:00
PMCR- 2021/04/28
CRDT- 2021/04/30 01:30
PHST- 2021/03/19 00:00 [received]
PHST- 2021/04/23 00:00 [revised]
PHST- 2021/04/24 00:00 [accepted]
PHST- 2021/04/30 01:30 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/09/23 06:00 [medline]
PHST- 2021/04/28 00:00 [pmc-release]
AID - biom11050650 [pii]
AID - biomolecules-11-00650 [pii]
AID - 10.3390/biom11050650 [doi]
PST - epublish
SO  - Biomolecules. 2021 Apr 28;11(5):650. doi: 10.3390/biom11050650.