TABLE 1.
Behavioral, structural, and molecular impacts following adolescent social isolation.
| Study | Strain (sex) | Isolation model (age of isolation onset) | Behavioral impacts (age of testing) | Structural impacts | Molecular impacts |
| Liu et al., 2019 | CD-1 mice (M) | GH (5/cage) or SI (PND 23) | ↑Soc affiliation, ↓soc rec, ↓soc memory (∼PND 93) | ||
| Zhang et al., 2021 | C57BL/6J mice (M) | GH (3/cage) or SI (PND 28) | ↓Soc pref, ↓soc rec (5-trial soc rec task, ∼PND 56) | ||
| Liu et al., 2015 | C57BL/6J mice (M) | GH (3–5/cage) or (PND 21–22) | ↓Soc interaction (∼4 weeks), ↑retention of fear memory (∼8 weeks) | ||
| Kercmar et al., 2011 | C57BL/6J mice (M&F) | GH (3/cage) or SI (PND 30–80 or PND 30–60) | ↓Soc rec, (PND 80) | ||
| Varlinskaya and Spear, 2008 | Sprague–Dawley rats (M&F) | GH (3/cage) or SI from PND 23–28, PND 30–35, PND 37–42, or PND 65–70 | Increased soc activity in familiar and unfamiliar testing situations at PND 28, increased soc activity only in unfamiliar testing situation at PND 35 and 42 | ||
| Skelly et al., 2015 | Long-Evans rats (M) | GH (4/cage) or SI (PND 28) | ↑Locomotion (OF, ∼PND 70), ↑anxiety-like behavior (OF, ∼PND 70), ↓fear extinction (∼PND 84), ↑intake (i-2BC, 20% EtOH) | ||
| Naert et al., 2011 | C57BL/6J mice (M) | GH (3/cage) or SI (PND 21) | ↑Locomotion (OF, ∼PND 70), delayed fear extinction (∼PND 175) | ||
| Bianchi et al., 2006 | Lister hooded rats (M) | GH (3–4/cage) or SI (PND 25-28) | ↑Locomotion (OF, PND 53–56), ↓NOR (PND 54–57) | ||
| Voikar et al., 2005 | C57BL/6J and DBA/2 mice (M) | GH (3/cage) or SI (PND 28) | ↑Locomotion (OF), ↑anxiety-like behavior (EPM), ↓NOR, ↓freezing in contextual fear conditioning (PND 84∼112) | ||
| McLean et al., 2010 | Lister hooded rats (F) | GH (5/cage) or SI (PND 21-23) | ↑Locomotion (OF), ↓NOR, only in 1 m and 1 h ITI, ↓set-shifting (∼9 weeks) | ||
| McCool and Chappell, 2009 | Long-Evans rats (M) | GH (4/cage) or SI (PND 28–32) | ↑Anxiety-like behavior (EPM, ∼10 weeks), ↑intake and pref (24 h-access 2BC, 5 days, 10% EtOH), ↑operant response rate and intake (2 weeks, 10% EtOH) | ||
| Chappell et al., 2013 | Long-Evans rats (M) | GH (4-5/cage) or SI (PND 28–78 or PND 63–78) | ↑Anxiety-like behavior (EPM, PND 72), ↑locomotion (OF, PND 74-78), ↑intake (24 h-access 2BC, 10% EtOH, PND 82–86 and i-2BC, 4 weeks, 20% EtOH, PND 89) | ||
| Koike et al., 2009 | ICR mice (M) | GH (5/cage) or SI (PND 21) | ↑Anxiety-like behavior (EPM), ↓NOR, ↓habituation to unfamiliar intruder (∼4 weeks) | ||
| Karkhanis et al., 2014 | Long-Evans rats (M) | GH (4/cage) or SI (PND 28) | ↑Anxiety-like behavior (EPM, PND 74–75) | ↑DA and NE response with acute EtOH (2 g/kg, i.p.) in NAc | |
| Yorgason et al., 2013 | Long-Evans rats (M) | GH (4/cage) or SI (PND 28–77 or PND 28–174) | ↑Anxiety-like behavior (EPM, PND 74 and PND 174) | ↑DA terminal release and reuptake rates in NAc | |
| Yorgason et al., 2016 | Long-Evans rats (M) | GH (4/cage) or SI (PND 28–77 or PND 28–174) | ↑DA terminal release and reuptake rates in NAc and dorsal medial striatum | ||
| Rivera-Irizarry et al., 2020 | C57BL/6J mice (M&F) | GH (5/cage) or SI (PND 28 or PND 70) | ↓Anxiety-like behavior (EPM, F only, PND 74), no diff in intake or pref (DID, 20–30% EtOH, PND 80–119), no memory deficits (NOR, PND 152), ↑soc interaction (PND 180) | ||
| Lopez and Laber, 2015 | C57BL/6J mice (M&F) | GH (4/cage) or SI ± enrichment (PND 21) | ↑Intake in SI mice without enrichment (c-2BC, 3 weeks, 15% EtOH, PND 60), ↓anxiety-like behavior (LDB, PND 60) | ||
| Lopez et al., 2011 | C57BL/6J mice (M&F) | GH (4/cage) or SI (PND 21–61 or PND 60–100) | ↑Intake (c-2BC, 2 weeks, 15% EtOH, PND 65 or PND 105) | ||
| Butler et al., 2014b | Long-Evans rats (F) | GH (4/cage) or SI (PND 28) | ↑Intake and pref at early timepoints (i-2BC, 7 weeks, 20% EtOH, PND 100) | ||
| Deehan et al., 2007 | Long-Evans rats (M) | GH (2/cage), enriched housing, or SI (PND 21) | ↑Responding and pref (operant, 10% EtOH, PND 111) | ||
| Advani et al., 2007 | C57BL/6J mice (M&F) | Maternal separation (PND 2–14), then GH (2/cage) or SI (PND 21–60) | ↑Intake in M; ↓intake in F, ↑pref (2BC Mon-Fri, 9 weeks, 5–20% EtOH, PND 60) | ||
| Thorsell et al., 2005 | Wistar rats (M) | GH (2/cage) or SI (PND 46) | No changes in intake (24 h access 2BC, 3 days, 10% EtOH, ∼13 weeks) | ||
| Heimer-McGinn et al., 2020 | Long-Evans rats (M) | GH (9/cage) or SI (PND 21) | ↓Acquisition and reversal learning (BM, PND 143, 428, or 672) | ||
| Ouchi et al., 2013 | ICR mice (M) | GH (5/cage) or SI (PND 28–35), then resocialized for 5 weeks) | ↓Contextual and conditional fear memory (∼9 weeks) | ||
| Bagheri et al., 2021 | NMRI mice (M) | GH (4/cage) or SI (PND 19–21) | ↓Freezing behavior, ↓spatial memory (Y-maze, MWM, ∼8 weeks) | ||
| Pais et al., 2019 | C57BL/6J mice (M&F) | GH (4/cage) or SI (PND 29) | ↓NOR (PND 63–65) | ||
| Pisu et al., 2011a | Sprague-Dawley rats (M) | GH (6–8/cage) or SI (PND 25–30) | ↑Spatial memory (MWM, PND 55–60) | ↑ CORT on 5th day of MWM training | |
| Lander et al., 2017 | C57BL/6J mice (M) | GH or SI (PND 38 or PND 60) | ↑Locomotion, ↑anxiety-like behavior (OF), ↑NOR, ↑soc pref, ↓reversal learning and set shifting (water T-maze, ∼PND 61 or 81) | ↑Glutamatergic tone in mPFC | |
| Wang et al., 2019 | Balb/c mice (M) | GH or SI (PND 21) | ↑Locomotion (OF), ↑swim speeds, ↓spatial memory (MWM, ∼28 weeks) | ↓plasticity through ↓LTP in hippocampus (∼28 weeks) | ↓ AMPAR, NMDAR, and PSD-95 protein in hippocampus (∼28 weeks) |
| Bibancos et al., 2007 | C57BL/6J mice (M) | GH or SI (PND 21) | ↑Locomotion (OF, EPM, LDB,∼6 weeks) | ↓5-HT receptor mRNA in PFC (∼6 weeks) | |
| Makinodan et al., 2012 | PLP-eGFP mice (M) | GH (4/cage), enriched-housing (8/cage) or SI (PND 21) | Memory deficits (non-matching-to-place task), ↓ soc interaction, no diff in locomotion (PND 50) | ↓PFC myelin-related mRNA (PND 65) | |
| Butler et al., 2014a | Long-Evans rats (M) | GH (4/cage) or SI (PND 28) | ↑Locomotion (OF, PND 78–79), ↑intake and pref (i-2BC, 6 weeks, 20% EtOH, PND 92–95) | Altered HPA axis function (PND 85–88) | |
| Weiss et al., 2004 | Sprague–Dawley rats (M&F) | GH or SI (PND 21) | ↑Anxiety-like behavior (EPM, M only), ↓contextual fear conditioning (∼16 weeks) | Changes to CORT response (M only, ∼16 weeks) | |
| Hinton et al., 2019 | Thy-1-YFP C57BL/6J mice (M&F) | GH (6–8/cage) or SI (PND 31) | ↑spine densities and PSD-95ir in OFC (PND 82) | GC insufficiency and ↓CNPase in cortico-striatal regions (PND 39) | |
| Quan et al., 2010 | Wistar rats (M) | GH (3–4/cage) or SI (PND 21) | ↓Spatial memory and reversal learning (MWM, ∼8 weeks) | ↓plasticity through ↓LTP in PFC (∼8 weeks) | |
| Liu et al., 2016 | C57BL/6 mice (M&F) | GH (3–4/cage) or SI (PND 35) | ↑Locomotion (OF), ↓freezing in contextual and tone fear conditioning (PND 57–61) | Altered structural connectivity (PND 57–61) | |
| Medendorp et al., 2018 | Thy1-GFP mice (M&F) | GH or SI (PND 21) | ↓Sociability (soc pref), ↑locomotion (OF, ∼PND 112) | Immature dendritic spines, unaltered spine density in mPFC, impaired plasticity through ↓LTP (∼PND 112) | |
| Cinini et al., 2014 | Marmoset non-human primates (M&F) | GH with family for 3 weeks, or SI for 1 or 3 weeks at 8–10 months of age | ↓ BrdU + cells in hippocampus, and a smaller percentage of these cells were co-labeled with DCX (8–10 months) | ||
| Lesscher et al., 2015 | Lister hooded rats (M) | GH (4/cage) or SI (PND 21–43, then 4 weeks of pair housing) | ↑Intake and pref at early timepoints (i-2BC, 6 weeks period after 6 weeks of re-socialization, 20% EtOH) | ||
| Han et al., 2011 | Sprague Dawley rats (M) | GH (3/cage) or SI (PND 21–34, then resocialized from 35 to 55) | ↓Reversal learning (MWM, ∼PND 55) | ||
| Ouchi et al., 2013 | ICR mice (M) | GH (5/cage) or SI (PND 28–35), then resocialized for 5 weeks) | ↓Contextual and conditional fear memory (∼9 weeks) | ||
| Biggio et al., 2019 | Sprague-Dawley rats (M) | GH (5/cage), SI (PND 21) or SI + re-socialized (PND 49–77) | ↓BrdU+ and Ki67 + cells (PND 78), ↓DCX + cells (PND 92), ↓spine density and branching, ↓mature, mushroom spines in DG (PND 77) | ||
| Li et al., 2019 | Sprague-Dawley rats (M) | GH (4/cage) or SI (PND 21–34, then resocialization from PND 35–55) | ↓Reversal learning (MWM, PND 55) | ||
| Talani et al., 2016 | C57BL/6J mice (M) | GH (4–6/cage) or SI (PND 21) | ↓neuronal excitability in DG | ||
| Silva-Gomez et al., 2003 | Sprague-Dawley rats (M) | GH (3/cage) or SI (PND 21–77) | ↑Locomotion (OF, PND 70) | ↓ proximal and distal spine density in mPFC layer III and hippocampal CA1; shorter dendritic length in CA1 only |
Drinking data presented as (drinking paradigm, length of drinking period, percentage EtOH, PND drinking began) unless specific PNDs were given for drinking period. GH, group-housed; SI, socially isolated; PND, postnatal day; M, males; F, females; soc, social; rec, recognition; pref, preference; EPM, elevated plus maze; LDB, light-dark box; OF, open field; BM, Barnes maze; MWM, Morris water maze; NOR, novel object recognition; ITI, inter-trial interval; i.p., intraperitoneal; i.g., intragastric; i-2BC, intermittent two-bottle choice; c-2BC, consecutive 2-bottle choice; DID, drinking in the dark; PFC, prefrontal cortex; mPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; NAc, nucleus accumbens; DG, dentate gyrus; GC, glucocorticoid; CORT, corticosterone; HPA, hypothalamic-pituitary-adrenal axis; DA, dopamine; 5-HT, serotonin; NE, norepinephrine; LTP, long-term potentiation.