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72 Spear, L. P. Adolescent alcohol exposure: are there separable vulnerable periods within adolescence? Phsyiol. Behav. 148, 122–130 (2015).

73 Day, A., Celio, M. A., Lisman, S. A., Johansen, G. E. & Spear, L. P. Acute and chronic effects of alcohol on trail making test performance among underage drinkers in a field setting. J. Stud. Alcohol Drugs 74, 635–641 (2013).

74 Acheson, S. K. et al. Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task. PLoS ONE 8, e77768 (2013).

75 Semenova, S. Attention, impulsivity, and cognitive flexibility in adult male rats exposed to ethanol binge during adolescence as measured in the five-choice serial reaction time task: the effects of task and ethanol challenges. Psychopharmacology 219, 433–442 (2012).

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78 Gass, J. T. et al. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood. Neuropsychopharmacology 39, 2570–2583 (2014). This study demonstrates that alcohol exposure during adolescence decreases cognitive flexibility and increases disinhibition when rats are later tested in adulthood.

79 Risher, M. L. et al. Long-term effects of chronic intermittent ethanol exposure in adolescent and adult rats: radial-arm maze performance and operant food reinforced responding. PLoS ONE 8, e62940 (2013).

80 Miller, K. M. et al. Behavioral inefficiency on a risky decision-making task in adulthood after adolescent intermittent ethanol exposure in rats. Sci. Rep. 7, 4680 (2017).

81 Varlinskaya, E. I., Truxell, E. M. & Spear, L. P. Chronic intermittent ethanol during adolescence: effects on social behavior and ethanol sensitivity in adulthood. Alcohol 48, 433–444 (2014). This study demonstrates that alcohol exposure during early-mid but not mid-late adolescence increases social anxiety-like behaviour in male (but not female) adult rats and results in the persistence of adolescent-typical social facilitatory effects of ethanol into adulthood.

82 Varlinskaya, E. I., Kim, E. U. & Spear, L. P. Chronic intermittent ethanol exposure during adolescence effects on stress-induced social alterations and social drinking in adulthood. Brain Res. 1654, 145–156 (2016).

83 Pandey, S. C., Sakharkar, A. J., Tang, L. & Zhang, H. Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. Neurobiol. Dis. 82, 607–619 (2015). This paper shows notable alterations in epigenetic regulation in the amygdala following adolescent alcohol exposure, with inhibition of these alterations in histone regulation attenuating the increases in anxiety and elevated alcohol intake seen in exposed animals in adulthood.

84 Sakharkar, A. J. et al. A role for histone acetylation mechanisms in adolescent exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood. Brain Struct. Funct. 221, 4691–4703 (2016). This study relates changes in epigenetic regulation (histone acetylation) to disruptions in neurogenesis and decreases in BDNF after adolescent alcohol exposure.

85 Torcaso, A., Asimes, A., Meagher, M. & Pak, T. R. Adolescent binge alcohol exposure increases risk assessment behaviors in male Wistar rats after exposure to an acute psychological stressor in adulthood. Psychoneuroendocrinology 76, 154–161 (2017).

86 Slawecki, C. J., Thorsell, A. & Ehlers, C. L. Long-term neurobehavioral effects of alcohol or nicotine exposure in adolescent animal models. Ann. NY Acad. Sci. 1021, 448–452 (2004).

87 Lee, K. M., Coehlo, M. A., Solton, N. R. & Szumlinski, K. K. Negative affect and excessive alcohol intake incubate during protracted withdrawal from binge-drinking in adolescent, but not adult, mice. Front. Psychol. 8, 1128 (2017).

88 Vetreno, R. P., Broadwater, M., Liu, W., Spear, L. P. & Crews, F. T. Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain. PLoS ONE 9, e113421 (2014).

89 Gilpin, N. W., Karanikas, C. A. & Richardson, H. N. Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats. PLoS ONE 7, e31466 (2012).

90 Desikan, A., Wills, D. N. & Ehlers, C. L. Ontogeny and adolescent alcohol exposure in Wistar rats: open field conflict, light/dark box and forced swim test. Pharmacol. Biochem. Behav. 122, 279–285 (2014).

91 Ehlers, C. L., Criado, J. R., Wills, D. N., Liu, W. & Crews, F. T. Periadolescent ethanol exposure reduces adult forebrain ChAT + IR neurons: correlation with behavioral pathology. Neuroscience 199, 33–45 (2011). This study observed that repeated exposure to alcohol vapour during adolescence disrupts cholinergic neurons in the basal forebrain in adulthood, with these decreases correlating with the amount of disinhibitory behaviour observed in these animals.

92 Ehlers, C. L., Liu, W., Wills, D. N. & Crews, F. T. Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood. Neuroscience 244, 1–15 (2013).

93 Doremus-Fitzwater, T. L., Varlinskaya, E. I. & Spear, L. P. Effects of pre-test manipulation on elevated plus-maze behavior in adolescent and adult male and female Sprague-Dawley rats. Pharmacol. Biochem. Behav. 92, 413–423 (2009).

94 Holly, K. S., Orndorff, C. O. & Murray, T. A. MATSAP: an automated analysis of stretch-attend posture in rodent behavioral experiments. Sci. Rep. 6, 31286 (2016).

95 Palm, S., Momeni, S., Lundberg, S., Nylander, I. & Roman, E. Risk-assessment and risk-taking behavior predict potassium-and amphetamine-induced dopamine response in the dorsal striatum of rats. Front. Behav. Neurosci. 8, 236 (2014).

96 Nasrallah, N. A. et al. Long-term risk preference and suboptimal decision making following adolescent alcohol use. Proc. Natl Acad. Sci. USA 106, 17600–17604 (2009).

97 Nasrallah, N. A. et al. Risk preference following adolescent alcohol use is associated with corrupted encoding of costs but not rewards by mesolimbic dopamine. Proc. Natl Acad. Sci. USA 108, 5466–5471 (2011).

98 Clark, J. J. et al. Altered risk-based decision making following adolescent alcohol use results from an imbalance in reinforcement learning in rats. PLoS ONE 7, e37357 (2012).

99 Boutros, N., Semenova, S., Liu, W., Crews, F. T. & Markou, A. Adolescent intermittent ethanol exposure is associated with increased risky choice & decrease of dopaminergic & cholinergic neuron markers in adult rats. Int. J. Neuropharmacol. 18, pyu003 (2015).

100 Schindler, A. G., Tsutsui, K. T. & Clark, J. J. Chronic alcohol intake during adolescence, but not adulthood, promotes persistent deficits in risk-based decision making. Alcohol. Clin. Exp. Res. 38, 1622–1629 (2014). This study demonstrates that rats exposed repeatedly to alcohol during adolescence exhibit later increases in risk preference when indexed via an operant probability discounting task.

101 Sanchez-Roige, S., Pena-Oliver, Y., Ripley, T. L. & Stephens, D. N. Repeated ethanol exposure during early and late adolescence: double dissociation of effects on waiting and choice impulsivity. Alcohol. Clin. Exp. Res. 38, 2579–2589 (2014).

102 Schlegel, A. & Barry, H. 3rd. Adolescence: An Anthropological Inquiry. 1st edn (Free Press, New York, 1991).

103 Rodd-Henricks, Z. A. et al. Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: I. Periadolescent exposure. Alcohol. Clin. Exp. Res. 26, 1632–1641 (2002).

104 Broadwater, M. A., Varlinskaya, E. I. & Spear, L. P. Effects of voluntary access to sweetened ethanol during adolescence on intake in adulthood. Alcohol. Clin. Exp. Res. 37, 1048–1055 (2013).

105 Wille-Bille, A., de Olmos, S., Marengo, L., Chiner, F. & Pautassi, R. M. Long-term ethanol self-administration induces ΔFosB in male and female adolescent, but not in adult, Wistar rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 74, 15–30 (2017).

106 Pascual, M., Boix, J., Felipo, V. & Guerri, C. Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in the adult rat. J. Neurochem. 108, 920–931 (2009). This paper reports increases in ethanol intake in adulthood following intermittent exposure to alcohol during adolescence, along with alterations in dopaminergic and glutamatergic neurotransmitter systems and histone acetylation in the mesolimbic system.

107 Alaux-Cantin, S. et al. Alcohol intoxications during adolescence increase motivation for alcohol in adult rats and induce neuroadaptations in the nucleus accumbens. Neuropharmacology 67, 521–531 (2013).

108 Rodd-Henricks, Z. A. et al. Effects of ethanol exposure on subsequent acquisition and extinction of ethanol self-administration and expression of alcohol-seeking behavior in adult alcohol-preferring (P) rats: II. Adult exposure. Alcohol. Clin. Exp. Res. 26, 1642–1652 (2002).

109 Slawecki, C. J. & Betancourt, M. Effects of adolescent ethanol exposure on ethanol consumption in adult rats. Alcohol 26, 23–30 (2002).

110 Vetter, C. S., Doremus-Fitzwater, T. L. & Spear, L. P. Time-course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions. Alcohol. Clin. Exp. Res. 31, 1159–1168 (2007).

111 Tambour, S., Brown, L. L. & Crabbe, J. C. Gender and age at drinking onset affect voluntary alcohol consumption but neither the alcohol deprivation effect nor the response to stress in mice. Alcohol. Clin. Exp. Res. 32, 100–106 (2008).

112 Carrara-Nascimento, P. F., Olive, M. F. & Camarini, R. Ethanol pre-exposure during adolescence or adulthood increases ethanol intake but ethanol-induced conditioned place preference is enhanced only when pre-exposure occurs in adolescence. Dev. Psychobiol. 56, 36–48 (2014).

113 Amodeo, L. R., Kneiber, D., Wills, D. N. & Ehlers, C. L. Alcohol drinking during adolescence increases consumptive responses to alcohol in adulthood in Wistar rats. Alcohol 59, 43–51 (2017).

114 Fullgrabe, M. W., Vengeliene, V. & Spanagel, R. Influence of age at drinking onset on the alcohol deprivation effect and stress-induced drinking in female rats. Pharmacol. Biochem. Behav. 86, 32–26 (2007).

115 Przybycien-Szymanska, M. M., Mott, N. N., Paul, C. R., Gillespie, R. A. & Pak, T. R. Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity. PLoS ONE 6, e18350 (2011).

116 Allen, C. D. et al. Exposure to alcohol during adolescence exerts long-term effects on stress response and the adult brain stress circuits. Neuroscience 339, 64–71 (2016).

117 DiLeo, A., Wright, K. M., Mangone, E. & McDannald, M. A. Alcohol gains access to appetitive learning through adolescent heavy drinking. Behav. Neurosci. 129, 371–379 (2015).

118 Maldonado-Devincci, A. M., Badanich, K. A. & Kirstein, C. L. Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry. Alcohol 44, 57–66 (2010).

119 White, A. M. & Swartzwelder, H. S. Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults. Recent Dev. Alcohol 17, 161–176 (2005).

120 Spear, L. P. Adolescents and alcohol: acute sensitivities, enhanced intake, and later consequences. Neurotoxicol. Teratol. 41, 51–59 (2013).

121 Spear, L. P. & Swartzwelder, H. S. Adolescent alcohol exposure and persistence of adolescent typical phenotypes into adulthood: a mini-review. Neurosci. Biobehav. Rev. 45, 1–8 (2014). This paper reviews evidence showing that adolescent exposure to alcohol sometimes results in the persistence of adolescent-typical phenotypes into adulthood that are evident behaviourally, electrophysiologically and in terms of adolescent-typical alcohol sensitivities.

122 White, A. M. et al. Chronic-intermittent ethanol exposure during adolescence prevents normal developmental changes in sensitivity to ethanol-induced motor impairments. Alcohol. Clin. Exp. Res. 26, 960–968 (2002).

123 Toalston, J. E. et al. Reinforcing properties and neurochemical response of ethanol within the posterior ventral tegmental area are enhanced in adulthood by periadolescent ethanol consumption. J. Pharmacol. Exp. Ther. 35, 317–326 (2014).

124 Saalfield, J. & Spear, L. P. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversion in rats. Dev. Cogn. Neurosci. 16, 174–182 (2015).

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134 Thayer, R. E., Callahan, T. J., Welland, B. J., Hutchison, K. E. & Bryan, A. D. Associations between fractional anisotropy and problematic alcohol use in juvenile justice-involved adolescents. Am. J. Drug Alcohol Abuse 39, 365–371 (2013).

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137 Tapert, S. F. et al. Blood oxygen level dependent response and spatial working memory in adolescents with alcohol use disorders. Alcohol. Clin. Exp. Res. 28, 1577–1586 (2004).

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