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

IF 4.3 2区 医学 Q1 NEUROSCIENCES
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
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引用次数: 0

Abstract

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.

早期社会隔离对雌雄马氏撒丁岛酒精偏好大鼠的糖皮质激素受体系统和觅酒行为产生不同影响
出生后发育过程中的不良早期生活经历会诱发应激系统发生长期的神经生物学变化,从而影响随后的行为,包括罹患酒精使用障碍的倾向。在此,我们将经过基因筛选的雌雄马氏撒丁岛酒精偏好大鼠(msP)和Wistar大鼠暴露于从出生后第14天(PND14)到PND21的轻度、反复的社会剥夺中,并研究了早期社会隔离(ESI)对糖皮质激素受体(GR)系统以及对成年后饮酒和酗酒倾向的影响。我们发现,ESI会导致雄性msP大鼠前额叶皮层(PFC)的GR基因和蛋白表达水平升高,而雌性msP大鼠则不会。在雌性 Wistars 大鼠中,ESI 导致 Nr3c1 mRNA 水平显著下调,GR 蛋白水平降低。在雄性和雌性 msP 大鼠中,PND35 的血浆皮质酮水平相似,且不受 ESI 的影响。雌性 Wistar 大鼠的皮质酮水平高于雄性,这与 ESI 无关。在酒精自我给药实验中,我们发现药理应激剂育亨宾(0.0、0.312、0.625 和 1.25 毫克/千克)会增加两个品系大鼠的酒精自我给药,与 ESI 无关。消退后,0.625 毫克/千克育亨宾可显著恢复雌性大鼠对酒精的寻求。ESI增强了雌性msP大鼠的恢复能力。总之,本研究结果表明,出生后第三周内反复的社会剥夺会影响 GR 的表达,其影响方式与品系和性别有关:这种影响可能至少部分导致了雌性 mSP 大鼠对育亨宾诱导的酒精寻求效应更加敏感。
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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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