TABLE 2.
Behavioral, structural, and molecular impacts following adolescent ethanol exposure.
| Study | Strain (sex) | Ethanol paradigm (age of exposure) | Behavioral impacts | Structural impacts | Molecular impacts |
| Acute ethanol exposure | |||||
| Varlinskaya and Spear, 2002 | Sprague Dawley rats (M&F) | Acute i.p., 0.25–4 g/kg, 12.6% EtOH, prior to testing (PND 35 or PND 70) | ↑Sensitivity to EtOH-induced social facilitation and ↓sensitivity to EtOH-suppression of social interactions (PND 35 > PND 70) | ||
| Varlinskaya and Spear, 2004 | Sprague Dawley rats (M&F) | Acute i.p., 0.25–1.75 g/kg, 12.6% EtOH, prior to testing (PND 28, 35, or 42) | ↑sensitivity to EtOH-induced social facilitation and ↓sensitivity to EtOH-suppression of social interactions (PND 28 > 35 and 42) | ||
| Raymond et al., 2019 | C57BL/6J mice (M) | Acute i.p., 0.25–1.6 g/kg, 3–19% EtOH (PND 31–33 or 10-weeks) | 0.25 g/kg EtOH alleviated social avoidance and no social suppression at higher EtOH | ||
| Lopez et al., 2003 | C57BL/6J mice (M) | Acute i.p. prior to task, 1.0 g/kg, 1.75 g/kg, or 2.5 g/kg EtOH (PND 34–35 or PND 70) | ↑Locomotion in adolescents (OF) | ||
| Hefner and Holmes, 2007 | C57BL/6J mice (M) | Acute i.p. prior to task, 1.5 g/kg (4, 6, or 8 weeks of age) | ↑Locomotion in adolescents (OF) | ||
| Stevenson et al., 2008 | DBA/2J mice (M) | Acute i.p. prior to task, 1.5–3 g/kg, 20% EtOH (PND 28 or PND 63) | ↑Locomotion in adolescents (OF) | ||
| Melon and Boehm, 2011 | C57BL/6J and DBA/2J mice (M&F) | Acute i.p., 2 g/kg, 20% EtOH (PND 28–32 or PND 60–80) | ↑Locomotion in adolescents (OF) | ||
| Subchronic ethanol exposure | |||||
| Coleman, He et al., 2011 | C57BL/6 mice (M) | Consecutive i.g., 5 g/kg, 25% EtOH (PND 28–37 or PND 88–97) | ↓Reversal learning (MWM, PND 63–72) | Decreased cholinergic and DA-related mRNA in whole brain (PND 38) | |
| Quoilin et al., 2014 | Swiss mice (F) | Consecutive i.p., 2.5 or 4 g/kg, 20% EtOH (PND 28–41 or PND 63–76) | ↑Locomotion (OF, acute i.p., 2.5 g/kg, 20% EtOH, PND 63) | ||
| Quoilin et al., 2012 | Swiss mice (F) | Consecutive i.p., 2.5 or 4 g/kg, 20% EtOH (PND 28–41) | ↑Locomotion (OF, acute i.p., 2.5 g/kg, 20% EtOH, PND 63) | ||
| Sircar and Sircar, 2005 | Sprague Dawley rats (M) | Consecutive i.p., 2 g/kg (PND 30–35 or PND 60–65) | ↓Spatial memory (MWM, 30 min after last dose, PND 35) and when retested (PND 44, 48, and 60) | ||
| Sircar et al., 2009 | Sprague Dawley rats (F) | Consecutive i.p., 2 g/kg (PND 30–35 or PND 60–65) | ↓Spatial memory (MWM, 30 min after last dose, PND 35) | ||
| Carrara-Nascimento et al., 2017 | Swiss mice (M) | Consecutive i.p., 2 g/kg, 20% EtOH (PND 30–45 or PND 70–85) | ↑Adult intake (3BC, DID, periods of withdrawals and re-exposures, 4–15% EtOH, PND 50–136) | ||
| Broadwater and Spear, 2013 | Sprague Dawley rats (M) | Intermittent i.g., 4 g/kg, 25% EtOH (PND 28–48 or PND 70–90) | ↓Retention in contextual fear conditioning in adulthood after early EtOH exposure | ||
| Varlinskaya et al., 2014 | Sprague Dawley rats (M&F) | Intermittent i.g., 3.5 g/kg, 25% EtOH (PND 25–45 or P45–P65) | ↓Social investigation and pref (M only, PND 70), EtOH-induced social facilitation (acute i.p., 0.5–1.0 g/kg, 12.6% EtOH, PND 70) | ||
| Varlinskaya et al., 2016 | Sprague Dawley rats (M&F) | Intermittent i.g., 3.5 g/kg, 25% EtOH (PND 25–45) | ↓Soc investigation and ↓soc pref (M only, PND 70 and 77) | Dysregulation of the HPA axis (no habituation to repeated restraint stress) | |
| Scheidt et al., 2015 | Wistar rats (M) | Intermittent i.g., 3 g/kg of 15% EtOH or 1 g/kg of 5% EtOH (PND 30–46) | No anxiety-like behavior (EPM, PND 64–65) | ||
| Broadwater et al., 2014 | Sprague Dawley rats (M) | Intermittent i.g., 4 g/kg (PND 28–48 or PND 70–90) | ↓DCX + cells in DG (PND 74) | ||
| Galaj et al., 2020 | Sprague Dawley rats (M) | Intermittent i.g., 4 g/kg, 25% EtOH (PND 28–45 or PND 70–88) | ↑Neuronal excitability and ↓spine density in prelimbic layer V (PND 109) | ||
| Wolstenholme et al., 2017 | DBA/2J mice (M&F) | Intermittent i.g., 4 g/kg, 25% EtOH (PND 29–42) | ↑Locomotion (OF, PND 43), ↑locomotion in F after acute EtOH (OF, PND 66), ↓NOR (PND 66+) | ↓Myelin-related mRNA (PND 43) | |
| Vetreno and Crews, 2015 | Wistar rats (M) | Intermittent i.g., 5 g/kg, 20% EtOH (PND 25–55) | ↓NOR (PND 163–165) | Persistently ↓ DCX+ and Ki67+ cells in dorsal and ventral hippocampus (PND 56–220) | |
| Vetreno and Crews, 2012 | Wistar rats (M) | Intermittent i.g., 5 g/kg, 20% EtOH (PND 25–55) | ↓Reversal learning (MWM, PND 70) | ||
| Vetreno et al., 2016 | Wistar rats (M) | Intermittent i.g., 5 g/kg, 20% EtOH (PND 25–55) | ↓NOR (PND 163–165), ↑anxiety-like behavior (LDB, PND 219) | ||
| Kipp et al., 2021 | Sprague Dawley rats (M&F) | Intermittent i.g., 5 g/kg, 20% EtOH (PND 25–55) | No spatial memory deficits (SA, EPM), No deficits in reversal learning (operant model, PND 55+) | ↑Branching of apical dendric trees in the OFC (PND 115–125) | |
| Liu and Crews, 2017 | Wistar rats (M) | Intermittent i.g., 5 g/kg, 25% EtOH (PND 25–54) | ↓BrdU+, Ki67+, DCX+, Sox2+, and Tbr2+ cells in DG (PND 95) | ||
| Coleman, Liu et al., 2014 | C57BL/6J mice (M&F) | Intermittent i.g., 5 g/kg, 25% EtOH (PND 28–37) | ↓Reversal learning (BM, PND 91) | ||
| Risher et al., 2015 | Sprague Dawley rats (M) | Intermittent i.g., 5 g/kg, 35% EtOH (PND 30–46) | ↑Density of immature and ↓density of mature spines and ↑likelihood of low stimulus LTP in CA1 (PND 70–75) | ||
| Mulholland et al., 2018 | Sprague Dawley rats (M) | Intermittent i.g., 5 g/kg, 35% EtOH (PND 30–46) | ↓Density of long and mushroom spines ↓volume and diameter of long and stubby spines and filopodia in DG (PND 70) | ||
| Pandey et al., 2015 | Sprague Dawley rats (M) | Intermittent i.p., 2 g/kg, 20% EtOH (PND 28–41) | ↑Anxiety-like behavior (LDB, EPM, PND 42) | ||
| Sakharkar et al., 2016 | Sprague Dawley rats (M) | Intermittent i.p., 2g/kg, 20% EtOH (PND 28-41) | ↑Anxiety-like behavior (LDB, PND 94) | ↓DCX+ and Ki67+ cells in DG (PND 92) | |
| Pascual et al., 2007 | Wistar rats (M) | Intermittent i.p., 3 g/kg, 25% EtOH (PND 25–38) | ↓NOR (PND 41 and 61) | ||
| Montesinos et al., 2014 | C57BL/6 mice (F) | Intermittent i.p., 3 g/kg, 25% EtOH (PND 30–43) | ↓NOR (PND 66+) | ↓Myelin-related mRNA (PND 44), altered myelin structure in PFC (PND 44 and 65) | |
| Montesinos et al., 2016 | C57BL/6 mice (F) | Intermittent i.p., 3 g/kg, 25% EtOH (PND 30–43) | ↑Adult pref (PND 66+), ↑anxiety-like behavior (OF, EPM, PND 66+) | ||
| Pascual et al., 2021 | C57BL/6J mice (M&F) | Intermittent i.p., 3 g/kg, 25% EtOH (PND 30–43) | ↓NOR (PND 46) | ↑Spine density in DG (thin spines in F and stubby spines in M, PND 44) | |
| Drinking in the Dark | |||||
| Szumlinski et al., 2019 | C57BL/6J mice (M&F) | 2, 3, or 4 BC, DID, 5–40% EtOH for 14 days (PND 28–29 or PND 56–58) | ↑Anxiety-like behavior (LDB, PND ∼72) | ||
| Lee et al., 2018 | C57BL/6J mice (M) | 3BC, DID, 10–40% EtOH (PND 28–42 or PND 56–70) | ↑Adult intake (3BC, DID, 10–40% EtOH, PND ∼71–76), ↑anxiety-like behavior (LDB, PND 70) | ||
| Lee et al., 2016 | C57BL/6J mice (M) | 4BC, DID, 5–40% EtOH (4–6 weeks or 8–10 weeks) | No memory deficits (NOR, 24 h after last drink), no anxiety-like behavior (marble burying, 48 h after last drink) | ||
| Lee et al., 2017 | C57BL/6J mice (M) | 4BC, DID, 5–40% EtOH (PND 28–42 or PND 56–70) | ↑Anxiety-like behavior (marble burying, PND 70), ↑adult intake (4BC, DID, 5–40% EtOH, PND ∼71–76) | ||
| Metten et al., 2011 | HS/Np or HDID-1 mice (M&F) | DID, 2-week period, 20% EtOH (3–4, 4–5, 5–6, 6–7, 7–8, or 8–9 weeks) | ↑Adult intake (DID, 4 days on, 3 days off, 2-week period, 4-15% EtOH, 9 weeks) | ||
| Younis et al., 2019 | C57BL/6J mice (M&F) | DID, 20% EtOH (PND 28–36 or PND 72–80) | ↑Adult intake and pref (DID, 20% EtOH and c-2BC, 5–15% EtOH, PND 72–80) | ||
| Moore et al., 2010 | C57BL/6J and DBA/2J mice (M&F) | DID, 20% EtOH (PND 28–42) | ↑Adult intake (C57B/6J only, DID, 20% EtOH, PND 63–77) | ||
| Marco et al., 2017 | Wistar rats (M&F) | DID, 20% EtOH (PND 28–52) | No anxiety-like behavior (EPM, PND 53), ↓NOR (PND 63) | ||
| Wolstenholme et al., 2020 | C57BL/6J and DBA/2J mice (M) | DID, 5 or 20% EtOH (PND 28–36) | ↑Adult intake (DID, 5% EtOH, PND 72–80) | ||
| 2-bottle choice drinking | |||||
| Lesscher et al., 2021 | Lister hooded rats (M) | i-2BC, 20% EtOH (PND 42-56) | ↑Adult intake (i-2BC, 8 weeks, 20% EtOH, PND 75) | ||
| Salling et al., 2018 | C57BL/6J mice (M) | i-2BC, 15% EtOH (∼PND 30–60) | No anxiety-like behavior (EPM, ∼PND 63), ↓memory (delayed non-match to sample in T-maze, PND 65–80), No increase in adult intake (i-2BC, 15% EtOH, PND 70–94) | ||
| Varlinskaya et al., 2015 | Sprague Dawley rats (M&F) | i-2BC, 10% EtOH, access occurred alone or with 4–5 littermates (PND 36–46 or PND 76–86) | ↓Intake in F when drinking alone, ↑intake in M when social drinking | ||
| Vapor exposure | |||||
| Jury et al., 2017 | C57BL/6 or Thy-1 mice (M) | CIE (4–6 or 8–10 weeks) | No changes in intake or pref (24-h access 2BC, 2-week period, 15% EtOH, ∼10 weeks) | ↓Spine density in infralimbic mPFC, adult mice had thinner thin spines and wider wide spines | |
| Gass et al., 2014 | Long–Evans rats (M) | Intermittent vapor exposure (PND 28–42) | ↑Self-admin (operant model, 10–20% EtOH, PND 65–90), ↓cognitive flexibility (set shifting, PND 90–130), ↓anxiety-like behavior (EPM, PND 90–130), ↑resistance to extinction of EtOH-seeking (PND 90–130) | ||
| Trantham-Davidson et al., 2017 | Long–Evans rats (M) | Intermittent vapor exposure (PND 28–42) | ↑Long thin spine density in layer V of the prelimbic mPFC in adulthood | Alteration of DA neurotransmission in the prelimbic mPFC in adulthood | |
| Amodeo et al., 2021 | Wistar rats (M) | Intermittent CIE, 95% EtOH (PND 22–57 or PND 91–126) | ↓Long spine density in primary motor cortex (PND 70), ↓immature spine density in primary visual cortex at all ages (PND 70 and PND 139) | ||
| Other | |||||
| Vargas et al., 2014 | Wistar rats (M) | Operant model, 8–10% sweetened EtOH (PND 28–42 and PND 78–130) | ↓Working memory (T-maze, PND 88–89) | ↓Myelin density in mPFC (PND 43) | |
| Strong et al., 2010 | C57BL/6J mice (M&F) | Scheduled high alcohol consumption, 21 days access (PND 26–28 or PND 58–71) | ↑Adult pref (c-2BC, 20% EtOH, PND 66–69 and 24 h access 2BC, 5% EtOH, PND 58–61), ↑adult intake [24 h access 2BC, 5% EtOH, (M&F) and 10% EtOH (F only), PND 58–61] | ||
Drinking data presented as (drinking paradigm, length of drinking period, percentage EtOH, PND drinking began) unless specific PNDs were given for drinking period. PND, postnatal day; M, males; F, females; i.p., intraperitoneal; i.g., intragastric; BC, bottle choice, i-2BC, intermittent two-bottle choice; c-2BC, consecutive 2-bottle choice; DID, drinking in the dark; soc, social; pref, preference; EPM, elevated plus maze; LDB, light-dark box; OF, open field; SA, spontaneous alternation; BM, Barnes maze; MWM, Morris water maze; NOR, novel object recognition; ITI, inter-trial interval; PFC, prefrontal cortex; mPFC, medial prefrontal cortex; OFC, orbitofrontal cortex; DG, dentate gyrus; HPA, hypothalamic-pituitary-adrenal axis; DA, dopamine; LTP, long-term potentiation.