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Spear LP. Assessment of adolescent neurotoxicity: rationale and methodological considerations. Neurotoxicol Teratol 2007;29:1-9.
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doi:10.1002/hipo.20665. This study was the first to show that alcohol's effects on neural stem cells may be the primary mechanism by which the hippocampus degenerates in adolescent alcohol use disorders. Notably, the effect of alcohol on neural stem cells may also underlie the enhanced vulnerability of the adolescent hippocampus to alcoholinduced neurodegeneration
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Morris SA, Eaves DW, Smith AR, Nixon K. Alcohol inhibition of neurogenesis: a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model. Hippocampus 2009; doi:10.1002/hipo.20665. This study was the first to show that alcohol's effects on neural stem cells may be the primary mechanism by which the hippocampus degenerates in adolescent alcohol use disorders. Notably, the effect of alcohol on neural stem cells may also underlie the enhanced vulnerability of the adolescent hippocampus to alcoholinduced neurodegeneration.
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Hippocampus
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Morris, S.A.1
Eaves, D.W.2
Smith, A.R.3
Nixon, K.4
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Acute ethanol withdrawal (hangover) and social behavior in adolescent and adult male and female sprague-dawley rats
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Varlinskaya EI, Spear LP. Acute ethanol withdrawal (hangover) and social behavior in adolescent and adult male and female Sprague-Dawley rats. Alcohol Clin Exp Res 2004;28:40-50.
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Adolescent but not adult rats exhibit ethanol-mediated appetitive second-order conditioning
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This important study adds to emerging data indicating that adolescents may experience greater reward in response to alcohol than adolescents. The increased sensitivity to alcohol's rewarding effects could contribute to increased susceptibility to alcoholism
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Pautassi RM, Myers M, Spear LP, et al. Adolescent but not adult rats exhibit ethanol-mediated appetitive second-order conditioning. Alcohol Clin Exp Res 2008;32:2016-2027. This important study adds to emerging data indicating that adolescents may experience greater reward in response to alcohol than adolescents. The increased sensitivity to alcohol's rewarding effects could contribute to increased susceptibility to alcoholism.
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Motivational systems in adolescence: Possible implications for age differences in substance abuse and other risk-taking behaviors
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Doremus-Fitzwater TL, Varlinskaya EI, Spear LP. Motivational systems in adolescence: possible implications for age differences in substance abuse and other risk-taking behaviors. Brain Cogn 2010;72:114-123.
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Brain Cogn
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Doremus-Fitzwater, T.L.1
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Spear, L.P.3
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21
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Adolescent and adult heart rate responses to self-administered ethanol
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Stimuli that activate the brain's dopamine reward system cause an increase in heart rate. The authors use this measure to determine the intensity of alcohol reward, showing that adolescents find acute alcohol more rewarding than adults
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Ristuccia RC, Spear LP. Adolescent and adult heart rate responses to self-administered ethanol. Alcohol Clin Exp Res 2008;32:1807-1815. Stimuli that activate the brain's dopamine reward system cause an increase in heart rate. The authors use this measure to determine the intensity of alcohol reward, showing that adolescents find acute alcohol more rewarding than adults.
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Stansfield KH, Kirstein CL. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood. Pharmacol Biochem Behav 2007;86:637-642.
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23
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Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry
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This work shows that exposure of an alcohol-näive adolescent animal to an alcohol-intoxicated peer increases alcohol-seeking behavior and repeated alcohol exposure during adolescence causes long-lasting behavioral changes that persist into adulthood. This is important because it shows that adolescents are more vulnerable to alcohol's behavioral effects that act to promote consumption
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Maldonado-Devincci AM, Badanich KA, Kirstein CL. Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry. Alcohol 2010;44:57-66. This work shows that exposure of an alcohol-näive adolescent animal to an alcohol-intoxicated peer increases alcohol-seeking behavior and repeated alcohol exposure during adolescence causes long-lasting behavioral changes that persist into adulthood. This is important because it shows that adolescents are more vulnerable to alcohol's behavioral effects that act to promote consumption.
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Maldonado-Devincci, A.M.1
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Acute effects of ethanol on social behavior of adolescent and adult rats: Role of familiarity of the test situation
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Varlinskaya EI, Spear LP. Acute effects of ethanol on social behavior of adolescent and adult rats: role of familiarity of the test situation. Alcohol Clin Exp Res 2002;26:1502-1511.
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Alcohol Clin. Exp. Res.
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Varlinskaya, E.I.1
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25
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56349165074
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Social interaction and partner familiarity differentially alter voluntary ethanol intake in adolescent male and female rats
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authors show that exposure of an alcohol-näive animal to an alcohol-intoxicated peer increases subsequent self-administration of alcohol by the observer, signifying the importance of peer influence in initiation of alcohol use in adolescents
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Maldonado AM, Finkbeiner LM, Kirstein CL. Social interaction and partner familiarity differentially alter voluntary ethanol intake in adolescent male and female rats. Alcohol 2008;42:641-648. The authors show that exposure of an alcohol-näive animal to an alcohol-intoxicated peer increases subsequent self-administration of alcohol by the observer, signifying the importance of peer influence in initiation of alcohol use in adolescents.
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Alcohol
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Maldonado, A.M.1
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Developmental neurocircuitry of motivation in adolescence: A critical period of addiction vulnerability
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Chambers RA, Taylor JR, Potenza MN. Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 2003;160:1041-1052.
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Chambers, R.A.1
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Potenza, M.N.3
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27
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Repeated ethanol exposure during adolescence alters the developmental trajectory of dopaminergic output from the nucleus accumbens septi
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This study found that repeated alcohol exposure increases basal dopamine levels, but decreases the magnitude of dopamine release when alcohol is administered during early adolescence. Decreased dopamine response to alcohol could enhance the drive to consume alcohol
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Philpot RM, Wecker L, Kirstein CL. Repeated ethanol exposure during adolescence alters the developmental trajectory of dopaminergic output from the nucleus accumbens septi. Int J Dev Neurosci 2009;27:805-815. This study found that repeated alcohol exposure increases basal dopamine levels, but decreases the magnitude of dopamine release when alcohol is administered during early adolescence. Decreased dopamine response to alcohol could enhance the drive to consume alcohol.
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Philpot, R.M.1
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Azam L, Chen Y, Leslie FM. Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons. Neuroscience 2007;144: 1347-1360.
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Philpot R, Kirstein C. Developmental differences in the accumbal dopaminergic response to repeated ethanol exposure. Ann N Y Acad Sci 2004;1021: 422-426.
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authors review ethanol's effects on the dopamine reward system focusing on the pharmacological action of ethanol on cholinergic and glycine receptors
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Soderpalm B, Lof E, Ericson M. Mechanistic studies of ethanol's interaction with the mesolimbic dopamine reward system. Pharmacopsychiatry 2009;42 (Suppl 1) :S87-S94. The authors review ethanol's effects on the dopamine reward system focusing on the pharmacological action of ethanol on cholinergic and glycine receptors.
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Soderpalm, B.1
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31
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58549107423
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Repeated Alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes Alcohol intake in the adult rat
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This study correlates adolescent alcohol exposure with adult consumption and provides intriguing data examining dopamine and glutamate release, neurotransmitter receptor expression, and epigenetics. Data suggest that repeated alcohol exposure during adolescence suppresses D2 receptor expression which could act to drive alcohol consumption and increase the risk for addiction
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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 2009;108:920-931. This study correlates adolescent alcohol exposure with adult consumption and provides intriguing data examining dopamine and glutamate release, neurotransmitter receptor expression, and epigenetics. Data suggest that repeated alcohol exposure during adolescence suppresses D2 receptor expression which could act to drive alcohol consumption and increase the risk for addiction.
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Pascual, M.1
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Blum K, Chen AL, Braverman ER, et al. Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat 2008;4:893-918.
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Neural mechanisms of addiction: The role of reward-related learning and memory
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Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci 2006;29:565-598.
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Hyman, S.E.1
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34
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Proteomic analysis demonstrates adolescent vulnerability to lasting hippocampal changes following chronic Alcohol consumption
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A classic proteomics approach is used to show that alcohol consumption during adolescence alters the expression of numerous proteins, lasting into adulthood
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HargreavesGA, Quinn H, Kashem MA, et al. Proteomic analysis demonstrates adolescent vulnerability to lasting hippocampal changes following chronic alcohol consumption. Alcohol Clin Exp Res 2009;33:86-94. A classic proteomics approach is used to show that alcohol consumption during adolescence alters the expression of numerous proteins, lasting into adulthood.
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Hargreaves, G.A.1
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Carpenter-Hyland EP, Chandler LJ. Adaptive plasticity of NMDA receptors and dendritic spines: implications for enhanced vulnerability of the adolescent brain to alcohol addiction. Pharmacol Biochem Behav 2007;86:200-208.
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Ethanol-induced social facilitation in adolescent rats: Role of endogenous activity at mu opioid receptors
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This work demonstrates that mu opioid receptors mediate alcohol-induced social facilitation in adolescents. Since this response is considered rewarding, pharmacological inhibition of mu opioid receptors may be a potential therapy aimed at reducing alcohol consumption in this age group
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Varlinskaya EI, Spear LP. Ethanol-induced social facilitation in adolescent rats: role of endogenous activity at mu opioid receptors. Alcohol Clin Exp Res 2009;33:991-1000. This work demonstrates that mu opioid receptors mediate alcohol-induced social facilitation in adolescents. Since this response is considered rewarding, pharmacological inhibition of mu opioid receptors may be a potential therapy aimed at reducing alcohol consumption in this age group.
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Alcohol Clin. Exp. Res.
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51049105699
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Nicotine and ethanol interact during adolescence: Effects on the central cholinergic systems
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This is the first study on the effect of alcohol on the developing adolescent cholinergic system and shows that alcohol enhances midbrain cholinergic innervation
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Ribeiro-Carvalho A, Lima CS, Filgueiras CC, et al. Nicotine and ethanol interact during adolescence: effects on the central cholinergic systems. Brain Res 2008;1232:48-60. This is the first study on the effect of alcohol on the developing adolescent cholinergic system and shows that alcohol enhances midbrain cholinergic innervation.
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Crews FT, Nixon K. Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol 2009;44:115-127.
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Medina KL, Schweinsburg AD, Cohen-Zion M, et al. Effects of alcohol and combined marijuana and alcohol use during adolescence on hippocampal volume and asymmetry. Neurotoxicol Teratol 2007;29:141-152.
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Prefrontal cortex volumes in adolescents with Alcohol use disorders: Unique gender effects
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This study demonstrates that adolescent alcohol consumption interferes with normal prefrontal cortex development, but the effects are sex-dependent. This is the first study to examine sex-specific structural effects of alcohol on the prefrontal cortex in human adolescents
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Medina KL, McQueeny T, Nagel BJ, et al. Prefrontal cortex volumes in adolescents with alcohol use disorders: unique gender effects. Alcohol Clin Exp Res 2008;32:386-394. This study demonstrates that adolescent alcohol consumption interferes with normal prefrontal cortex development, but the effects are sex-dependent. This is the first study to examine sex-specific structural effects of alcohol on the prefrontal cortex in human adolescents.
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authors describe the balance between impulsivity and executive function and how alcohol damages the frontal cortex, tipping the scale towards impulsive behavior. Increased sensitivity of adolescents to this damage and its potential consequences are discussed in this insightful review
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Crews FT, Boettiger CA. Impulsivity, frontal lobes and risk for addiction. Pharmacol Biochem Behav 2009;93:237-247. The authors describe the balance between impulsivity and executive function and how alcohol damages the frontal cortex, tipping the scale towards impulsive behavior. Increased sensitivity of adolescents to this damage and its potential consequences are discussed in this insightful review.
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