Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats

Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcoho...

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Main Authors: F. Benvenuti, S. De Carlo, L. Rullo, L. Caffino, L.M. Losapio, C. Morosini, M. Ubaldi, L. Soverchia, N. Cannella, E. Domi, S. Candeletti, F. Mottarlini, L. Fattore, P. Romualdi, F. Fumagalli, V. Trezza, M. Roberto, R. Ciccocioppo
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:Neurobiology of Stress
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352289523000863
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author F. Benvenuti
S. De Carlo
L. Rullo
L. Caffino
L.M. Losapio
C. Morosini
M. Ubaldi
L. Soverchia
N. Cannella
E. Domi
S. Candeletti
F. Mottarlini
L. Fattore
P. Romualdi
F. Fumagalli
V. Trezza
M. Roberto
R. Ciccocioppo
author_facet F. Benvenuti
S. De Carlo
L. Rullo
L. Caffino
L.M. Losapio
C. Morosini
M. Ubaldi
L. Soverchia
N. Cannella
E. Domi
S. Candeletti
F. Mottarlini
L. Fattore
P. Romualdi
F. Fumagalli
V. Trezza
M. Roberto
R. Ciccocioppo
author_sort F. Benvenuti
collection DOAJ
description Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of Nr3c1 mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.
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spelling doaj.art-e9e4db9997264d94b1f298ac2b50339b2024-02-02T04:39:33ZengElsevierNeurobiology of Stress2352-28952024-01-0128100598Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring ratsF. Benvenuti0S. De Carlo1L. Rullo2L. Caffino3L.M. Losapio4C. Morosini5M. Ubaldi6L. Soverchia7N. Cannella8E. Domi9S. Candeletti10F. Mottarlini11L. Fattore12P. Romualdi13F. Fumagalli14V. Trezza15M. Roberto16R. Ciccocioppo17School of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, ItalySchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, ItalyDepartment of Pharmacological and Biomolecular Sciences, ‘Rodolfo Paoletti’, University of Milan, Milan, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, ItalySchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, ItalySchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, ItalySchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, ItalySchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, ItalyDepartment of Pharmacological and Biomolecular Sciences, ‘Rodolfo Paoletti’, University of Milan, Milan, ItalyCNR Institute of Neuroscience-Cagliari, National Research Council, Cagliari, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, ItalyDepartment of Pharmacological and Biomolecular Sciences, ‘Rodolfo Paoletti’, University of Milan, Milan, ItalyDepartment of Science, University “Roma Tre”, Rome, ItalyDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USASchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino, Italy; Corresponding author. University of Camerino School of Pharmacy, Center for Neuroscience, section Pharmacology 622032 Camerino, MC, Italy.Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of Nr3c1 mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.http://www.sciencedirect.com/science/article/pii/S2352289523000863AlcoholismRewardGlucocorticoid receptorAlcohol drinkingStressRelapse
spellingShingle F. Benvenuti
S. De Carlo
L. Rullo
L. Caffino
L.M. Losapio
C. Morosini
M. Ubaldi
L. Soverchia
N. Cannella
E. Domi
S. Candeletti
F. Mottarlini
L. Fattore
P. Romualdi
F. Fumagalli
V. Trezza
M. Roberto
R. Ciccocioppo
Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats
Neurobiology of Stress
Alcoholism
Reward
Glucocorticoid receptor
Alcohol drinking
Stress
Relapse
title Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats
title_full Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats
title_fullStr Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats
title_full_unstemmed Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats
title_short Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats
title_sort early social isolation differentially affects the glucocorticoid receptor system and alcohol seeking behavior in male and female marchigian sardinian alcohol preferring rats
topic Alcoholism
Reward
Glucocorticoid receptor
Alcohol drinking
Stress
Relapse
url http://www.sciencedirect.com/science/article/pii/S2352289523000863
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