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. Author manuscript; available in PMC: 2022 Jun 15.
Published in final edited form as: Neuropharmacology. 2021 Apr 13;191:108567. doi: 10.1016/j.neuropharm.2021.108567

Table 3:

Summary of studies examining the long-lasting effect of maternal separation on development of CRF and OT systems.

Reference Species Sex Maternal Separation Duration Maternal Separation Age Measurement Age Result
Babygirija et al., 2012 Sprague-Dawley rats Male 3 hr/day PND 2–14 >PND 56 (following restraint stress) ↑ CRF mRNA in PVN
↑ CRF neurons in PVN
Flagel et al., 2003 Sprague-Dawley rats Female and male 10 min/day Early (PND 2–8) Late (PND 8–14) PND 70 ↔ CRF mRNA in PVN and Amyg
Garcia-Gutiérrez etal., 2016 Swiss ICR mice Male 12 hr/day PND 8 and 12 PND 28 ↑ CRF mRNA in PVN
de Almeida Magalhães et al., 2018 C57BL/6 mice Female and male 6 hr/day PND 5–21 PND 45 ↔ CRF mRNA in Hypo
↑ CRF1 and CRF2 receptor mRNA in Hipp
Slotten et al., 2006 Long-Evans rats Male 3 hr/day PND 3–15 PND 115–120 ↔ CRF mRNA in PVN
Desbonnet et al., 2008 Wistar rats Female and male 3 hr/day PND 2–14 Adulthood (stressed vs. control) ↑ CRF neurons in PVN (stressed females only)
↓ CRF neurons in Amyg (males only)
Wang et al., 2014 Sprague-Dawley rats Female and male 3 hr/day PND 1–10 PND 77 ↑ CRF mRNA in Hipp
↑ CRF protein in Hipp
Murgatroyd et al., 2009 C57BL/6N mice Male 3 hr/day PND 1–10 PND 90 ↔ CRF mRNA in Hypo
Plotsky et al., 2005 Long-Evans rats Female and male Short 15 min/day
Long 3 hr/day
PND 2–14 PND 100–120 ↑ CRF in CSF (MS Long only)
↑ CRF mRNA and protein in PVN, Amyg, BNST and LC (MS Long only)
↑ CRF total receptor binding in PVN and LC (MS Long only)
↓ CRF total receptor binding in PVN and LC (MS Short only)
↑ CRF1 receptor binding and mRNA in PVN and LC (MS Long only)
↓ CRF1 receptor binding and mRNA in Ctx (MS Long only)
Aisa et al., 2008 Wistar rats Females 3 hr/day PND 2–21 PND 60–75 ↑ CRF mRNA in PVN
O’Malley et al., 2011 Sprague-Dawley rats Male 3 hr/day PND 2–21 Adulthood ↑ CRF1 protein in Hypo
↔ CRF1 protein in PFC, Amyg or Hipp
↔ CRF2 protein in Hypo, Amyg or Hipp
Ladd et al., 1996 Sprague-Dawley rats Male 4–6 hr/day PND 2–20 PND 114–115 ↓ CRF receptor binding in Pit
↑ CRF receptor binding in RN.
↑ CRF in ME, PB and RN
Plotsky and Meaney, 1993 Long-Evans rats Female and male 3 hr/day PND 2–14 PND 90–120 ↑ CRF mRNA and content in Hypo
Chen et al., 2012 Sprague-Dawley rats Female and male 4 hr/day PND 2–13 PND 60 ↑ CRF mRNA in Hypo (females only)
↔ CRF mRNA in Amyg
Bravo et al., 2011 Sprague-Dawley rats Female and male 3 hr/day PND 2–14 PND 77–91 ↑ CRF1 mRNA in Amyg and RN
↔ CRF1 mRNA in Hipp
↓ CRF2 mRNA in Hipp, Amyg and RN
Hu et al., 2020 C57BL/6J Male 24 hr PND 3 PND 70–84 ↑ CRF neurons in BNST
↑ CRF mRNA in BNST
↑ CRF1 receptor mRNA in BNST
↔ CRF2 receptor mRNA in BNST
He et al., 2018 Mandarin voles Female 15 min/day PND 1–14 Adulthood ↔ OT cells in PVN and SON
Gilles and Poston, 2017 Sprague-Dawley rats Female and male 4 hr/day PND 2–21 PND 103–107 ↔ OT cells in PVN and SON
Riveros-Barrera and Duenas, 2016 Wistar rats Female and male 3 hr/day PND 1–21 1) PND 35
2) PND 90
1) ↔ OT in plasma
2) ↑ OT in plasma (females)
 ↓ OT in plasma (males)
Babygirija et al., 2012 Sprague-Dawley rats Male 3 hr/day PND 2–14 >PND 56 (following restraint stress) ↓ OT mRNA in PVN
↓ OT magno cells in PVN
↔ OT parvo cells in PVN
Tsuda et al., 2011 C57BL/6J mice Male 3 hr/day PND 1–14 PND 28–42 ↑ OT cells in PVN
Barrett et al., 2015 Prairie voles Female 3 hr/day PND 1–14 PND 98 ↔ OT receptors
Wei et al., 2020 Sprague-Dawley rats Male 4 hr/day PND 1–20 PND 42 ↓ OT receptor mRNA in PFC
↓ OT receptor protein in PFC
Holubová et al., 2019 Wistar rats Female and male 3 hr/day PND 1–21 PND 30 ↓ OT in plasma
Lukas et al., 2010 Wistar rats Male 3 hr/day PND 1–14 1) PND 35
2) PND 56
3) PND 112
1) ↓ OT receptors in Ctx
2) ↓ OT receptors in Ctx
3) ↓ OT receptors in Sep and Str
 ↑ OT receptors in VMH
Veenema et al., 2007 C57BL/6 mice Female and male 3 hr/day PND 1–14 >PND 98 ↓ OT parvo cells in PVN (females only)
↔ OT magno cells in PVN
Oreland et al., 2010 Wistar rats Male Short 15 min/day
Long 6 hr/day
PND 1–21 1) PND 21

2) PND 70
1) ↓ OT in Hypo (MS Short only)
 ↓ OT in Amyg
 ↑ OT in Pit (MS Short only)
2) ↔ OT in Hypo and Pit
 ↓ OT Amyg (MS Short only)
Melchior et al., 2018 Wistar rats Female and male 3 hr/day PND 2–12 PND 56 ↔ OT receptor mRNA in SC

Abbreviations: Amyg=amydala; BNST=bed nucleus of the stria terminalis; CRF=corticotropin-releasing hormone; CSF=cerebrospinal fluid; Ctx=cortex; Hipp=hippocampus; Hypo=hypothalamus; LC=locus coeruleus; ME=median eminence; mRNA=messenger ribonucleic acid; OT=oxytocin; PB=parabrachial nucleus; PFC=prefrontal cortex; Pit=pituitary; PND=postnatal day; PVN=paraventricular nucleus; RN=raphe nucleus; SC=spinal cord; Sep=septum; SON=supraoptic nucleus; Str=striatum; VMH=ventromedial hypothalamus