, Volume 206, Issue 1, pp 1–21 | Cite as

Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models

  • Nicole L. Schramm-Sapyta
  • Q. David Walker
  • Joseph M. Caster
  • Edward D. Levin
  • Cynthia M. Kuhn


Background and rationale

Epidemiological evidence suggests that people who begin experimenting with drugs of abuse during early adolescence are more likely to develop substance use disorders (SUDs), but this correlation does not guarantee causation. Animal models, in which age of onset can be tightly controlled, offer a platform for testing causality. Many animal models address drug effects that might promote or discourage drug intake and drug-induced neuroplasticity.


We have reviewed the preclinical literature to investigate whether adolescent rodents are differentially sensitive to rewarding, reinforcing, aversive, locomotor, and withdrawal-induced effects of drugs of abuse.

Results and conclusions

The rodent model literature consistently suggests that the balance of rewarding and aversive effects of drugs of abuse is tipped toward reward in adolescence. However, increased reward does not consistently lead to increased voluntary intake: age effects on voluntary intake are drug and method specific. On the other hand, adolescents are consistently less sensitive to withdrawal effects, which could protect against compulsive drug seeking. Studies examining neuronal function have revealed several age-related effects but have yet to link these effects to vulnerability to SUDs. Taken together, the findings suggest factors which may promote recreational drug use in adolescents, but evidence relating to pathological drug-seeking behavior is lacking. A call is made for future studies to address this gap using behavioral models of pathological drug seeking and for neurobiologic studies to more directly link age effects to SUD vulnerability.


Addiction Alcohol Cocaine Amphetamine Nicotine Cannabinoids 


  1. Aberg M, Wade D, Wall E, Izenwasser S (2007) Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats. Neurotoxicol Teratol 29:37–46PubMedCrossRefGoogle Scholar
  2. Abraham HD, Fava M (1999) Order of onset of substance abuse and depression in a sample of depressed outpatients. Compr Psychiatry 40:44–50PubMedCrossRefGoogle Scholar
  3. Abreu ME, Bigelow GE, Fleisher L, Walsh SL (2001) Effect of intravenous injection speed on responses to cocaine and hydromorphone in humans. Psychopharmacology (Berl) 154:76–84CrossRefGoogle Scholar
  4. Acheson SK, Stein RM, Swartzwelder HS (1998) Impairment of semantic and figural memory by acute ethanol: age-dependent effects. Alcohol Clin Exp Res 22:1437–1442PubMedCrossRefGoogle Scholar
  5. Acheson SK, Richardson R, Swartzwelder HS (1999) Developmental changes in seizure susceptibility during ethanol withdrawal. Alcohol 18:23–26PubMedCrossRefGoogle Scholar
  6. Acheson SK, Ross EL, Swartzwelder HS (2001) Age-independent and dose-response effects of ethanol on spatial memory in rats. Alcohol 23:167–175PubMedCrossRefGoogle Scholar
  7. Adriani W, Laviola G (2003) Elevated levels of impulsivity and reduced place conditioning with d-amphetamine: two behavioral features of adolescence in mice. Behav Neurosci 117:695–703PubMedCrossRefGoogle Scholar
  8. Adriani W, Chiarotti F, Laviola G (1998) Elevated novelty seeking and peculiar d-amphetamine sensitization in periadolescent mice compared with adult mice. Behav Neurosci 112:1152–1166PubMedCrossRefGoogle Scholar
  9. Adriani W, Deroche-Gamonet V, Le Moal M, Laviola G, Piazza PV (2006) Preexposure during or following adolescence differently affects nicotine-rewarding properties in adult rats. Psychopharmacology (Berl) 184:382–390CrossRefGoogle Scholar
  10. Aharonovich E, Hasin DS, Brooks AC, Liu X, Bisaga A, Nunes EV (2006) Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug Alcohol Depend 81:313–322PubMedCrossRefGoogle Scholar
  11. Aizenstein ML, Segal DS, Kuczenski R (1990) Repeated amphetamine and fencamfamine: sensitization and reciprocal cross-sensitization. Neuropsychopharmacology 3:283–290PubMedGoogle Scholar
  12. American Psychiatric Association (1994) Diagnostic and statistical manual for mental disorders (DSM-IV). American Psychiatric Association, PhiladelphiaGoogle Scholar
  13. Andersen SL (2003) Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27:3–18PubMedCrossRefGoogle Scholar
  14. Andersen SL (2005) Stimulants and the developing brain. Trends Pharmacol Sci 26:237–243PubMedCrossRefGoogle Scholar
  15. Andersen SL, Gazzara RA (1993) The ontogeny of apomorphine-induced alterations of neostriatal dopamine release: effects on spontaneous release. J Neurochem 61:2247–2255PubMedCrossRefGoogle Scholar
  16. Andersen SL, Teicher MH (2000) Sex differences in dopamine receptors and their relevance to ADHD. Neurosci Biobehav Rev 24:137–141PubMedCrossRefGoogle Scholar
  17. Andersen SL, Thompson AP, Krenzel E, Teicher MH (2002) Pubertal changes in gonadal hormones do not underlie adolescent dopamine receptor overproduction. Psychoneuroendocrinology 27:683–691PubMedCrossRefGoogle Scholar
  18. Arizzi MN, Correa M, Betz AJ, Wisniecki A, Salamone JD (2003) Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats: studies with low and high rate operant schedules. Behav Brain Res 147:203–210PubMedCrossRefGoogle Scholar
  19. Babbini M, Davis WM (1972) Time–dose relationships for locomotor activity effects of morphine after acute or repeated treatment. Br J Pharmacol 46:213–224PubMedGoogle Scholar
  20. Badanich KA, Adler KJ, Kirstein CL (2006) Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi. Eur J Pharmacol 550:95–106PubMedCrossRefGoogle Scholar
  21. Balda MA, Anderson KL, Itzhak Y (2006) Adolescent and adult responsiveness to the incentive value of cocaine reward in mice: role of neuronal nitric oxide synthase (nNOS) gene. Neuropharmacology 51:341–349PubMedCrossRefGoogle Scholar
  22. Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153:31–43CrossRefGoogle Scholar
  23. Bardo MT, Cain ME, Bylica KE (2006) Effect of amphetamine on response inhibition in rats showing high or low response to novelty. Pharmacol Biochem Behav 85:98–104PubMedCrossRefGoogle Scholar
  24. Barr CS, Schwandt ML, Newman TK, Higley JD (2004) The use of adolescent nonhuman primates to model human alcohol intake: neurobiological, genetic, and psychological variables. Ann N Y Acad Sci 1021:221–233PubMedCrossRefGoogle Scholar
  25. Bell RL, Rodd ZA, Sable HJ, Schultz JA, Hsu CC, Lumeng L, Murphy JM, McBride WJ (2006) Daily patterns of ethanol drinking in peri-adolescent and adult alcohol-preferring (P) rats. Pharmacol Biochem Behav 83:35–46PubMedCrossRefGoogle Scholar
  26. Belluzzi JD, Lee AG, Oliff HS, Leslie FM (2004) Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats. Psychopharmacology (Berl) 174:389–395CrossRefGoogle Scholar
  27. Belluzzi JD, Wang R, Leslie FM (2005) Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats. Neuropsychopharmacology 30:705–712PubMedCrossRefGoogle Scholar
  28. Bergstrom HC, McDonald CG, French HT, Smith RF (2008) Continuous nicotine administration produces selective, age-dependent structural alteration of pyramidal neurons from prelimbic cortex. Synapse 62:31–39PubMedCrossRefGoogle Scholar
  29. Beveridge TJ, Gill KE, Hanlon CA, Porrino LJ (2008) Review. Parallel studies of cocaine-related neural and cognitive impairment in humans and monkeys. Philos Trans R Soc Lond B Biol Sci 363:3257–3266PubMedCrossRefGoogle Scholar
  30. Bolanos CA, Glatt SJ, Jackson D (1998) Subsensitivity to dopaminergic drugs in periadolescent rats: a behavioral and neurochemical analysis. Brain Res Dev Brain Res 111:25–33PubMedCrossRefGoogle Scholar
  31. Brenhouse HC, Andersen SL (2008) Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults. Behav Neurosci 122:460–465PubMedCrossRefGoogle Scholar
  32. Brenhouse HC, Sonntag KC, Andersen SL (2008) Transient D1 dopamine receptor expression on prefrontal cortex projection neurons: relationship to enhanced motivational salience of drug cues in adolescence. J Neurosci 28:2375–2382PubMedCrossRefGoogle Scholar
  33. Brielmaier JM, McDonald CG, Smith RF (2007) Immediate and long-term behavioral effects of a single nicotine injection in adolescent and adult rats. Neurotoxicol Teratol 29:74–80PubMedCrossRefGoogle Scholar
  34. Brown TL, Flory K, Lynam DR, Leukefeld C, Clayton RR (2004) Comparing the developmental trajectories of marijuana use of African American and Caucasian adolescents: patterns, antecedents, and consequences. Exp Clin Psychopharmacol 12:47–56PubMedCrossRefGoogle Scholar
  35. Brunell SC, Spear LP (2005) Effect of stress on the voluntary intake of a sweetened ethanol solution in pair-housed adolescent and adult rats. Alcohol Clin Exp Res 29:1641–1653PubMedCrossRefGoogle Scholar
  36. Burke JD Jr, Burke KC, Rae DS (1994) Increased rates of drug abuse and dependence after onset of mood or anxiety disorders in adolescence. Hosp Community Psychiatry 45:451–455PubMedGoogle Scholar
  37. Buxbaum DM, Yarbrough GG, Carter ME (1973) Biogenic amines and narcotic effects. I. Modification of morphine-induced analgesia and motor activity after alteration of cerebral amine levels. J Pharmacol Exp Ther 185:317–327PubMedGoogle Scholar
  38. Camarini R, Griffin WC 3rd, Yanke AB, Rosalina dos Santos B, Olive MF (2008) Effects of adolescent exposure to cocaine on locomotor activity and extracellular dopamine and glutamate levels in nucleus accumbens of DBA/2J mice. Brain Res 1193:34–42PubMedCrossRefGoogle Scholar
  39. Campbell JO, Wood RD, Spear LP (2000) Cocaine and morphine-induced place conditioning in adolescent and adult rats. Physiol Behav 68:487–493PubMedCrossRefGoogle Scholar
  40. Cao J, Belluzzi JD, Loughlin SE, Keyler DE, Pentel PR, Leslie FM (2007a) Acetaldehyde, a major constituent of tobacco smoke, enhances behavioral, endocrine, and neuronal responses to nicotine in adolescent and adult rats. Neuropsychopharmacology 32:2025–2035PubMedCrossRefGoogle Scholar
  41. Cao J, Lotfipour S, Loughlin SE, Leslie FM (2007b) Adolescent maturation of cocaine-sensitive neural mechanisms. Neuropsychopharmacology 32:2279–2289PubMedCrossRefGoogle Scholar
  42. Carr GD, Fibiger HC, Phillips AC (1989) Conditioned place preference as a measure of drug reward. In: Liebman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Clarendon, Oxford, pp 264–319Google Scholar
  43. Caster JM, Kuhn CM (2009) Maturation of coordinated immediate early gene expression by cocaine during adolescence. Neuroscience 160:13–31PubMedCrossRefGoogle Scholar
  44. Caster JM, Walker QD, Kuhn CM (2005) Enhanced behavioral response to repeated-dose cocaine in adolescent rats. Psychopharmacology (Berl) 183:218–225CrossRefGoogle Scholar
  45. Caster JM, Walker QD, Kuhn CM (2007) A single high dose of cocaine induces differential sensitization to specific behaviors across adolescence. Psychopharmacology (Berl) 193:247–260CrossRefGoogle Scholar
  46. Cha YM, White AM, Kuhn CM, Wilson WA, Swartzwelder HS (2006) Differential effects of delta9-THC on learning in adolescent and adult rats. Pharmacol Biochem Behav 83:448–455PubMedCrossRefGoogle Scholar
  47. Cha YM, Jones KH, Kuhn CM, Wilson WA, Swartzwelder HS (2007) Sex differences in the effects of delta9-tetrahydrocannabinol on spatial learning in adolescent and adult rats. Behav Pharmacol 18:563–569PubMedCrossRefGoogle Scholar
  48. Chambers RA, Taylor JR, Potenza MN (2003) Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 160:1041–1052PubMedCrossRefGoogle Scholar
  49. Chen K, Kandel DB (1995) The natural history of drug use from adolescence to the mid-thirties in a general population sample. Am J Public Health 85:41–47PubMedCrossRefGoogle Scholar
  50. Chen K, Kandel DB, Davies M (1997) Relationships between frequency and quantity of marijuana use and last year proxy dependence among adolescents and adults in the United States. Drug Alcohol Depend 46:53–67PubMedCrossRefGoogle Scholar
  51. Chen H, Matta SG, Sharp BM (2007) Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug. Neuropsychopharmacology 32:700–709PubMedCrossRefGoogle Scholar
  52. Cheng RK, MacDonald CJ, Meck WH (2006) Differential effects of cocaine and ketamine on time estimation: implications for neurobiological models of interval timing. Pharmacol Biochem Behav 85:114–122PubMedCrossRefGoogle Scholar
  53. Collins SL, Izenwasser S (2002) Cocaine differentially alters behavior and neurochemistry in periadolescent versus adult rats. Brain Res Dev Brain Res 138:27–34PubMedCrossRefGoogle Scholar
  54. Collins SL, Izenwasser S (2004) Chronic nicotine differentially alters cocaine-induced locomotor activity in adolescent vs. adult male and female rats. Neuropharmacology 46:349–362PubMedCrossRefGoogle Scholar
  55. Collins SL, Montano R, Izenwasser S (2004) Nicotine treatment produces persistent increases in amphetamine-stimulated locomotor activity in periadolescent male but not female or adult male rats. Brain Res Dev Brain Res 153:175–187PubMedCrossRefGoogle Scholar
  56. Compton WM 3rd, Cottler LB, Phelps DL, Ben Abdallah A, Spitznagel EL (2000) Psychiatric disorders among drug dependent subjects: are they primary or secondary? Am J Addict 9:126–134PubMedCrossRefGoogle Scholar
  57. Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A (2003) Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry 60:837–844PubMedCrossRefGoogle Scholar
  58. Counotte DS, Spijker S, Van de Burgwal LH, Hogenboom F, Schoffelmeer AN, De Vries TJ, Smit AB, Pattij T (2009) Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats. Neuropsychopharmacology 34:299–306PubMedCrossRefGoogle Scholar
  59. Crair MC, Malenka RC (1995) A critical period for long-term potentiation at thalamocortical synapses. Nature 375:325–328PubMedCrossRefGoogle Scholar
  60. Cruz FC, Delucia R, Planeta CS (2005) Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats. Pharmacol Biochem Behav 80:411–417PubMedCrossRefGoogle Scholar
  61. Cunningham MG, Bhattacharyya S, Benes FM (2002) Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence. J Comp Neurol 453:116–130PubMedCrossRefGoogle Scholar
  62. Cunningham MG, Bhattacharyya S, Benes FM (2008) Increasing Interaction of amygdalar afferents with GABAergic interneurons between birth and adulthood. Cereb Cortex 18:1529–1535PubMedCrossRefGoogle Scholar
  63. Dawes MA, Antelman SM, Vanyukov MM, Giancola P, Tarter RE, Susman EJ, Mezzich A, Clark DB (2000) Developmental sources of variation in liability to adolescent substance use disorders. Drug Alcohol Depend 61:3–14PubMedCrossRefGoogle Scholar
  64. de Wit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology (Berl) 75:134–143CrossRefGoogle Scholar
  65. de Wit H, Bodker B, Ambre J (1992) Rate of increase of plasma drug level influences subjective response in humans. Psychopharmacology (Berl) 107:352–358CrossRefGoogle Scholar
  66. Depoortere RY, Li DH, Lane JD, Emmett-Oglesby MW (1993) Parameters of self-administration of cocaine in rats under a progressive-ratio schedule. Pharmacol Biochem Behav 45:539–548PubMedCrossRefGoogle Scholar
  67. Deroche-Gamonet V, Belin D, Piazza PV (2004) Evidence for addiction-like behavior in the rat. Science 305:1014–1017PubMedCrossRefGoogle Scholar
  68. DeWit DJ, Hance J, Offord DR, Ogborne A (2000) The influence of early and frequent use of marijuana on the risk of desistance and of progression to marijuana-related harm. Prev Med 31:455–464PubMedCrossRefGoogle Scholar
  69. Deykin EY, Levy JC, Wells V (1987) Adolescent depression, alcohol and drug abuse. Am J Public Health 77:178–182PubMedCrossRefGoogle Scholar
  70. Di Chiara G (1995) The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 38:95–137PubMedCrossRefGoogle Scholar
  71. Doremus TL, Brunell SC, Varlinskaya EI, Spear LP (2003) Anxiogenic effects during withdrawal from acute ethanol in adolescent and adult rats. Pharmacol Biochem Behav 75:411–418PubMedCrossRefGoogle Scholar
  72. Doremus TL, Brunell SC, Rajendran P, Spear LP (2005) Factors influencing elevated ethanol consumption in adolescent relative to adult rats. Alcohol Clin Exp Res 29:1796–1808PubMedCrossRefGoogle Scholar
  73. Earleywine M (1993a) Hangover moderates the association between personality and drinking problems. Addict Behav 18:291–297PubMedCrossRefGoogle Scholar
  74. Earleywine M (1993b) Personality risk for alcoholism covaries with hangover symptoms. Addict Behav 18:415–420PubMedCrossRefGoogle Scholar
  75. Egerton A, Brett RR, Pratt JA (2005) Acute delta9-tetrahydrocannabinol-induced deficits in reversal learning: neural correlates of affective inflexibility. Neuropsychopharmacology 30:1895–1905PubMedCrossRefGoogle Scholar
  76. Egerton A, Allison C, Brett RR, Pratt JA (2006) Cannabinoids and prefrontal cortical function: insights from preclinical studies. Neurosci Biobehav Rev 30:680–695PubMedCrossRefGoogle Scholar
  77. Ehrlich ME, Sommer J, Canas E, Unterwald EM (2002) Periadolescent mice show enhanced DeltaFosB upregulation in response to cocaine and amphetamine. J Neurosci 22:9155–9159PubMedGoogle Scholar
  78. Elliott BM, Faraday MM, Phillips JM, Grunberg NE (2004) Effects of nicotine on elevated plus maze and locomotor activity in male and female adolescent and adult rats. Pharmacol Biochem Behav 77:21–28PubMedCrossRefGoogle Scholar
  79. Ernst M, Nelson EE, Jazbec S, McClure EB, Monk CS, Leibenluft E, Blair J, Pine DS (2005) Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents. Neuroimage 25:1279–1291PubMedCrossRefGoogle Scholar
  80. Ernst M, Pine DS, Hardin M (2006) Triadic model of the neurobiology of motivated behavior in adolescence. Psychol Med 36:299–312PubMedCrossRefGoogle Scholar
  81. Eshel N, Nelson EE, Blair RJ, Pine DS, Ernst M (2007) Neural substrates of choice selection in adults and adolescents: development of the ventrolateral prefrontal and anterior cingulate cortices. Neuropsychologia 45:1270–1279PubMedCrossRefGoogle Scholar
  82. Evenden JL (1999) Varieties of impulsivity. Psychopharmacology (Berl) 146:348–361CrossRefGoogle Scholar
  83. Evenden J, Ko T (2005) The psychopharmacology of impulsive behaviour in rats VIII: effects of amphetamine, methylphenidate, and other drugs on responding maintained by a fixed consecutive number avoidance schedule. Psychopharmacology (Berl) 180:294–305CrossRefGoogle Scholar
  84. Faraday MM, Elliott BM, Phillips JM, Grunberg NE (2003) Adolescent and adult male rats differ in sensitivity to nicotine’s activity effects. Pharmacol Biochem Behav 74:917–931PubMedCrossRefGoogle Scholar
  85. Fitzgerald LW, Nestler EJ (1995) Molecular and cellular adaptations in signal transduction pathways following ethanol exposure. Clin Neurosci 3:165–173PubMedGoogle Scholar
  86. Franken IH, Hendriks VM (2000) Early-onset of illicit substance use is associated with greater axis-II comorbidity, not with axis-I comorbidity. Drug Alcohol Depend 59:305–308PubMedCrossRefGoogle Scholar
  87. Frantz KJ, O’Dell LE, Parsons LH (2007) Behavioral and neurochemical responses to cocaine in periadolescent and adult rats. Neuropsychopharmacology 32:625–637PubMedCrossRefGoogle Scholar
  88. Fullgrabe MW, Vengeliene V, Spanagel R (2007) Influence of age at drinking onset on the alcohol deprivation effect and stress-induced drinking in female rats. Pharmacol Biochem Behav 86:320–326PubMedCrossRefGoogle Scholar
  89. Gaiardi M, Bartoletti M, Bacchi A, Gubellini C, Costa M, Babbini M (1991) Role of repeated exposure to morphine in determining its affective properties: place and taste conditioning studies in rats. Psychopharmacology (Berl) 103:183–186CrossRefGoogle Scholar
  90. Gelbard HA, Teicher MH, Faedda G, Baldessarini RJ (1989) Postnatal development of dopamine D1 and D2 receptor sites in rat striatum. Brain Res Dev Brain Res 49:123–130PubMedCrossRefGoogle Scholar
  91. George O, Mandyam CD, Wee S, Koob GF (2008) Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments. Neuropsychopharmacology 33:2474–2482PubMedCrossRefGoogle Scholar
  92. Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159:1642–1652PubMedCrossRefGoogle Scholar
  93. Gossop M, Griffiths P, Powis B, Strang J (1992) Severity of dependence and route of administration of heroin, cocaine and amphetamines. Br J Addict 87:1527–1536PubMedCrossRefGoogle Scholar
  94. Grueter BA, Gosnell HB, Olsen CM, Schramm-Sapyta NL, Nekrasova T, Landreth GE, Winder DG (2006) Extracellular-signal regulated kinase 1-dependent metabotropic glutamate receptor 5-induced long-term depression in the bed nucleus of the stria terminalis is disrupted by cocaine administration. J Neurosci 26:3210–3219PubMedCrossRefGoogle Scholar
  95. Grueter BA, McElligott ZA, Winder DG (2007) Group I mGluRs and long-term depression: potential roles in addiction? Mol Neurobiol 36:232–244PubMedCrossRefGoogle Scholar
  96. Haertzen CA, Kocher TR, Miyasato K (1983) Reinforcements from the first drug experience can predict later drug habits and/or addiction: results with coffee, cigarettes, alcohol, barbiturates, minor and major tranquilizers, stimulants, marijuana, hallucinogens, heroin, opiates and cocaine. Drug Alcohol Depend 11:147–165PubMedCrossRefGoogle Scholar
  97. Helms CM, Reeves JM, Mitchell SH (2006) Impact of strain and d-amphetamine on impulsivity (delay discounting) in inbred mice. Psychopharmacology (Berl) 188:144–151CrossRefGoogle Scholar
  98. Hill SY, Shen S, Lowers L, Locke J (2000) Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism. Biol Psychiatry 48:265–275PubMedCrossRefGoogle Scholar
  99. Hodos W (1961) Progressive ratio as a measure of reward strength. Science 134:943–944PubMedCrossRefGoogle Scholar
  100. Hoffmann JP, Su SS (1998) Parental substance use disorder, mediating variables and adolescent drug use: a non-recursive model. Addiction 93:1351–1364PubMedCrossRefGoogle Scholar
  101. Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2:695–703PubMedCrossRefGoogle Scholar
  102. Infurna RN, Spear LP (1979) Developmental changes in amphetamine-induced taste aversions. Pharmacol Biochem Behav 11:31–35PubMedCrossRefGoogle Scholar
  103. Izumi Y, Zorumski CF (1995) Developmental changes in long-term potentiation in CA1 of rat hippocampal slices. Synapse 20:19–23PubMedCrossRefGoogle Scholar
  104. Jerome A, Sanberg PR (1987) The effects of nicotine on locomotor behavior in non-tolerant rats: a multivariate assessment. Psychopharmacology (Berl) 93:397–400CrossRefGoogle Scholar
  105. Kalivas PW, O’Brien C (2008) Drug addiction as a pathology of staged neuroplasticity. Neuropsychopharmacology 33:166–180PubMedCrossRefGoogle Scholar
  106. Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev 16:223–244PubMedCrossRefGoogle Scholar
  107. Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162:1403–1413PubMedCrossRefGoogle Scholar
  108. Kalivas PW, Widerlov E, Stanley D, Breese G, Prange AJ Jr (1983) Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamine-independent increase in locomotor activity. J Pharmacol Exp Ther 227:229–237PubMedGoogle Scholar
  109. Kantak KM, Goodrich CM, Uribe V (2007) Influence of sex, estrous cycle, and drug-onset age on cocaine self-administration in rats (Rattus norvegicus). Exp Clin Psychopharmacol 15:37–47PubMedCrossRefGoogle Scholar
  110. Kerstetter KA, Kantak KM (2007) Differential effects of self-administered cocaine in adolescent and adult rats on stimulus-reward learning. Psychopharmacology (Berl) 194:403–411CrossRefGoogle Scholar
  111. Kirkwood A, Lee HK, Bear MF (1995) Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience. Nature 375:328–331PubMedCrossRefGoogle Scholar
  112. Knackstedt LA, Kalivas PW (2007) Extended access to cocaine self-administration enhances drug-primed reinstatement but not behavioral sensitization. J Pharmacol Exp Ther 322:1103–1109PubMedCrossRefGoogle Scholar
  113. Kolta MG, Scalzo FM, Ali SF, Holson RR (1990) Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats. Psychopharmacology (Berl) 100:377–382CrossRefGoogle Scholar
  114. Koob GF (1996) Drug addiction: the yin and yang of hedonic homeostasis. Neuron 16:893–896PubMedCrossRefGoogle Scholar
  115. Koob GF (2009) Neurobiological substrates for the dark side of compulsivity in addiction. Neuropharmacology 56(Suppl 1):18–31PubMedCrossRefGoogle Scholar
  116. Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58PubMedCrossRefGoogle Scholar
  117. Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129PubMedCrossRefGoogle Scholar
  118. Kosofsky BE, Genova LM, Hyman SE (1995) Postnatal age defines specificity of immediate early gene induction by cocaine in developing rat brain. J Comp Neurol 351:27–40PubMedCrossRefGoogle Scholar
  119. Kota D, Martin BR, Robinson SE, Damaj MI (2007) Nicotine dependence and reward differ between adolescent and adult male mice. J Pharmacol Exp Ther 322:399–407PubMedCrossRefGoogle Scholar
  120. Kreek MJ, Nielsen DA, Butelman ER, LaForge KS (2005) Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nat Neurosci 8:1450–1457PubMedCrossRefGoogle Scholar
  121. Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DE, Truong HT, Russo SJ, Laplant Q, Sasaki TS, Whistler KN, Neve RL, Self DW, Nestler EJ (2005) Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48:303–314PubMedCrossRefGoogle Scholar
  122. Land C, Spear NE (2004) Ethanol impairs memory of a simple discrimination in adolescent rats at doses that leave adult memory unaffected. Neurobiol Learn Mem 81:75–81PubMedCrossRefGoogle Scholar
  123. Lanier LP, Isaacson RL (1977) Early developmental changes in the locomotor response to amphetamine and their relation to hippocampal function. Brain Res 126:567–575PubMedCrossRefGoogle Scholar
  124. Laviola G, Wood RD, Kuhn C, Francis R, Spear LP (1995) Cocaine sensitization in periadolescent and adult rats. J Pharmacol Exp Ther 275:345–357PubMedGoogle Scholar
  125. Laviola G, Adriani W, Terranova ML, Gerra G (1999) Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models. Neurosci Biobehav Rev 23:993–1010PubMedCrossRefGoogle Scholar
  126. Laviola G, Pascucci T, Pieretti S (2001) Striatal dopamine sensitization to d-amphetamine in periadolescent but not in adult rats. Pharmacol Biochem Behav 68:115–124PubMedCrossRefGoogle Scholar
  127. Le Houezec J, Halliday R, Benowitz NL, Callaway E, Naylor H, Herzig K (1994) A low dose of subcutaneous nicotine improves information processing in non-smokers. Psychopharmacology (Berl) 114:628–634CrossRefGoogle Scholar
  128. Lee EH, Ma YL (1995) Amphetamine enhances memory retention and facilitates norepinephrine release from the hippocampus in rats. Brain Res Bull 37:411–416PubMedCrossRefGoogle Scholar
  129. Lenroot RK, Giedd JN (2006) Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neurosci Biobehav Rev 30:718–729PubMedCrossRefGoogle Scholar
  130. Leslie FM, Loughlin SE, Wang R, Perez L, Lotfipour S, Belluzzia JD (2004) Adolescent development of forebrain stimulant responsiveness: insights from animal studies. Ann N Y Acad Sci 1021:148–159PubMedCrossRefGoogle Scholar
  131. Levin ED (1992) Nicotinic systems and cognitive function. Psychopharmacology (Berl) 108:417–431CrossRefGoogle Scholar
  132. Levin ED, Simon BB (1998) Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology (Berl) 138:217–230CrossRefGoogle Scholar
  133. Levin ED, Rezvani AH, Montoya D, Rose JE, Swartzwelder HS (2003) Adolescent-onset nicotine self-administration modeled in female rats. Psychopharmacology (Berl) 169:141–149CrossRefGoogle Scholar
  134. Levin ED, Lawrence SS, Petro A, Horton K, Rezvani AH, Seidler FJ, Slotkin TA (2007) Adolescent vs. adult-onset nicotine self-administration in male rats: duration of effect and differential nicotinic receptor correlates. Neurotoxicol Teratol 29:458–465PubMedCrossRefGoogle Scholar
  135. Lewinsohn PM, Rohde P, Brown RA (1999) Level of current and past adolescent cigarette smoking as predictors of future substance use disorders in young adulthood. Addiction 94:913–921PubMedCrossRefGoogle Scholar
  136. Liao D, Malinow R (1996) Deficiency in induction but not expression of LTP in hippocampal slices from young rats. Learn Mem 3:138–149PubMedCrossRefGoogle Scholar
  137. Little PJ, Kuhn CM, Wilson WA, Swartzwelder HS (1996) Differential effects of ethanol in adolescent and adult rats. Alcohol Clin Exp Res 20:1346–1351PubMedCrossRefGoogle Scholar
  138. Lopez M, Simpson D, White N, Randall C (2003) Age- and sex-related differences in alcohol and nicotine effects in C57BL/6J mice. Addict Biol 8:419–427PubMedCrossRefGoogle Scholar
  139. Lu W, Wolf ME (1999) Repeated amphetamine administration alters AMPA receptor subunit expression in rat nucleus accumbens and medial prefrontal cortex. Synapse 32:119–131PubMedCrossRefGoogle Scholar
  140. Lu W, Chen H, Xue CJ, Wolf ME (1997) Repeated amphetamine administration alters the expression of mRNA for AMPA receptor subunits in rat nucleus accumbens and prefrontal cortex. Synapse 26:269–280PubMedCrossRefGoogle Scholar
  141. Lu W, Monteggia LM, Wolf ME (1999) Withdrawal from repeated amphetamine administration reduces NMDAR1 expression in the rat substantia nigra, nucleus accumbens and medial prefrontal cortex. Eur J Neurosci 11:3167–3177PubMedCrossRefGoogle Scholar
  142. Lynskey MT, Heath AC, Bucholz KK, Slutske WS, Madden PA, Nelson EC, Statham DJ, Martin NG (2003) Escalation of drug use in early-onset cannabis users vs co-twin controls. Jama 289:427–433PubMedCrossRefGoogle Scholar
  143. Majchrowicz E (1975) Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43:245–254PubMedCrossRefGoogle Scholar
  144. Maldonado AM, Kirstein CL (2005) Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats. Physiol Behav 86:568–572PubMedCrossRefGoogle Scholar
  145. Mantsch JR, Baker DA, Francis DM, Katz ES, Hoks MA, Serge JP (2008) Stressor- and corticotropin releasing factor-induced reinstatement and active stress-related behavioral responses are augmented following long-access cocaine self-administration by rats. Psychopharmacology (Berl) 195:591–603CrossRefGoogle Scholar
  146. Markwiese BJ, Acheson SK, Levin ED, Wilson WA, Swartzwelder HS (1998) Differential effects of ethanol on memory in adolescent and adult rats. Alcohol Clin Exp Res 22:416–421PubMedGoogle Scholar
  147. Martinez JL Jr, Jensen RA, Messing RB, Vasquez BJ, Soumireu-Mourat B, Geddes D, Liang KC, McGaugh JL (1980) Central and peripheral actions of amphetamine on memory storage. Brain Res 182:157–166PubMedCrossRefGoogle Scholar
  148. McAlonan K, Brown VJ (2003) Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behav Brain Res 146:97–103PubMedCrossRefGoogle Scholar
  149. McCarthy LE, Mannelli P, Niculescu M, Gingrich K, Unterwald EM, Ehrlich ME (2004) The distribution of cocaine in mice differs by age and strain. Neurotoxicol Teratol 26:839–848PubMedCrossRefGoogle Scholar
  150. McDonald CG, Eppolito AK, Brielmaier JM, Smith LN, Bergstrom HC, Lawhead MR, Smith RF (2007) Evidence for elevated nicotine-induced structural plasticity in nucleus accumbens of adolescent rats. Brain Res 1151:211–218PubMedCrossRefGoogle Scholar
  151. McDougall SA, Duke MA, Bolanos CA, Crawford CA (1994) Ontogeny of behavioral sensitization in the rat: effects of direct and indirect dopamine agonists. Psychopharmacology (Berl) 116:483–490CrossRefGoogle Scholar
  152. McGue M, Iacono WG, Legrand LN, Elkins I (2001a) Origins and consequences of age at first drink. II. Familial risk and heritability. Alcohol Clin Exp Res 25:1166–1173PubMedCrossRefGoogle Scholar
  153. McGue M, Iacono WG, Legrand LN, Malone S, Elkins I (2001b) Origins and consequences of age at first drink. I. Associations with substance-use disorders, disinhibitory behavior and psychopathology, and P3 amplitude. Alcohol Clin Exp Res 25:1156–1165PubMedCrossRefGoogle Scholar
  154. Meng SZ, Ozawa Y, Itoh M, Takashima S (1999) Developmental and age-related changes of dopamine transporter, and dopamine D1 and D2 receptors in human basal ganglia. Brain Res 843:136–144PubMedCrossRefGoogle Scholar
  155. Meyer JM, Neale MC (1992) The relationship between age at first drug use and teenage drug use liability. Behavior Genetics 22:197–213PubMedCrossRefGoogle Scholar
  156. Moghaddam B, Homayoun H (2008) Divergent plasticity of prefrontal cortex networks. Neuropsychopharmacology 33:42–55PubMedCrossRefGoogle Scholar
  157. Montague DM, Lawler CP, Mailman RB, Gilmore JH (1999) Developmental regulation of the dopamine D1 receptor in human caudate and putamen. Neuropsychopharmacology 21:641–649PubMedCrossRefGoogle Scholar
  158. Nelson RA, Boyd SJ, Ziegelstein RC, Herning R, Cadet JL, Henningfield JE, Schuster CR, Contoreggi C, Gorelick DA (2006) Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans. Drug Alcohol Depend 82:19–24PubMedCrossRefGoogle Scholar
  159. Nestler EJ (1994) Molecular neurobiology of drug addiction. Neuropsychopharmacology 11:77–87PubMedGoogle Scholar
  160. Nestler EJ, Berhow MT, Brodkin ES (1996) Molecular mechanisms of drug addiction: adaptations in signal transduction pathways. Mol Psychiatry 1:190–199PubMedGoogle Scholar
  161. Obernier JA, White AM, Swartzwelder HS, Crews FT (2002) Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav 72:521–532PubMedCrossRefGoogle Scholar
  162. O’Dell LE (2009) A psychobiological framework of the substrates that mediate nicotine use during adolescence. Neuropharmacology 56(Suppl 1):263–278PubMedCrossRefGoogle Scholar
  163. O’Dell LE, Bruijnzeel AW, Smith RT, Parsons LH, Merves ML, Goldberger BA, Richardson HN, Koob GF, Markou A (2006) Diminished nicotine withdrawal in adolescent rats: implications for vulnerability to addiction. Psychopharmacology (Berl) 186:612–619CrossRefGoogle Scholar
  164. O’Dell LE, Chen SA, Smith RT, Specio SE, Balster RL, Paterson NE, Markou A, Zorrilla EP, Koob GF (2007a) Extended access to nicotine self-administration leads to dependence: circadian measures, withdrawal measures, and extinction behavior in rats. J Pharmacol Exp Ther 320:180–193PubMedCrossRefGoogle Scholar
  165. O’Dell LE, Torres OV, Natividad LA, Tejeda HA (2007b) Adolescent nicotine exposure produces less affective measures of withdrawal relative to adult nicotine exposure in male rats. Neurotoxicol Teratol 29:17–22PubMedCrossRefGoogle Scholar
  166. O’Shea M, Singh ME, McGregor IS, Mallet PE (2004) Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. J Psychopharmacol 18:502–508PubMedCrossRefGoogle Scholar
  167. Paine TA, Dringenberg HC, Olmstead MC (2003) Effects of chronic cocaine on impulsivity: relation to cortical serotonin mechanisms. Behav Brain Res 147:135–147PubMedCrossRefGoogle Scholar
  168. Palacios JM, Camps M, Cortes R, Probst A (1988) Mapping dopamine receptors in the human brain. J Neural Transm Suppl 27:227–235PubMedGoogle Scholar
  169. Partridge JG, Tang KC, Lovinger DM (2000) Regional and postnatal heterogeneity of activity-dependent long-term changes in synaptic efficacy in the dorsal striatum. J Neurophysiol 84:1422–1429PubMedGoogle Scholar
  170. Parylak SL, Caster JM, Walker QD, Kuhn CM (2008) Gonadal steroids mediate the opposite changes in cocaine-induced locomotion across adolescence in male and female rats. Pharmacol Biochem Behav 89:314–323PubMedCrossRefGoogle Scholar
  171. Pattij T, Wiskerke J, Schoffelmeer AN (2008) Cannabinoid modulation of executive functions. Eur J Pharmacol 585:458–463PubMedCrossRefGoogle Scholar
  172. Patton GC, McMorris BJ, Toumbourou JW, Hemphill SA, Donath S, Catalano RF (2004) Puberty and the onset of substance use and abuse. Pediatrics 114:e300–e306PubMedCrossRefGoogle Scholar
  173. Perry JL, Anderson MM, Nelson SE, Carroll ME (2007) Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake. Physiol Behav 91:126–133PubMedCrossRefGoogle Scholar
  174. Pert A, Sivit C (1977) Neuroanatomical focus for morphine and enkephalin-induced hypermotility. Nature 265:645–647PubMedCrossRefGoogle Scholar
  175. Philpot RM, Badanich KA, Kirstein CL (2003) Place conditioning: age-related changes in the rewarding and aversive effects of alcohol. Alcohol Clin Exp Res 27:593–599PubMedGoogle Scholar
  176. Popke EJ, Allen SR, Paule MG (2000) Effects of acute ethanol on indices of cognitive-behavioral performance in rats. Alcohol 20:187–192PubMedCrossRefGoogle Scholar
  177. Prat G, Adan A, Perez-Pamies M, Sanchez-Turet M (2008) Neurocognitive effects of alcohol hangover. Addict Behav 33:15–23PubMedCrossRefGoogle Scholar
  178. Prescott CA, Kendler KS (1999) Age at first drink and risk for alcoholism: a noncausal association. Alcohol Clin Exp Res 23:101–107PubMedGoogle Scholar
  179. Provost SC, Woodward R (1991) Effects of nicotine gum on repeated administration of the Stroop test. Psychopharmacology (Berl) 104:536–540CrossRefGoogle Scholar
  180. Quinn HR, Matsumoto I, Callaghan PD, Long LE, Arnold JC, Gunasekaran N, Thompson MR, Dawson B, Mallet PE, Kashem MA, Matsuda-Matsumoto H, Iwazaki T, McGregor IS (2008) Adolescent rats find repeated Delta(9)-THC less aversive than adult rats but display greater residual cognitive deficits and changes in hippocampal protein expression following exposure. Neuropsychopharmacology 33:1113–1126PubMedCrossRefGoogle Scholar
  181. Rajendran P, Spear LP (2004) The effects of ethanol on spatial and nonspatial memory in adolescent and adult rats studied using an appetitive paradigm. Ann N Y Acad Sci 1021:441–444PubMedCrossRefGoogle Scholar
  182. Rasmussen K, Beitner-Johnson DB, Krystal JH, Aghajanian GK, Nestler EJ (1990) Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J Neurosci 10:2308–2317PubMedGoogle Scholar
  183. Rethy CR, Smith CB, Villarreal JE (1971) Effects of narcotic analgesics upon the locomotor activity and brain catecholamine content of the mouse. J Pharmacol Exp Ther 176:472–479PubMedGoogle Scholar
  184. Rezvani AH, Levin ED (2004) Adolescent and adult rats respond differently to nicotine and alcohol: motor activity and body temperature. Int J Dev Neurosci 22:349–354PubMedCrossRefGoogle Scholar
  185. Ristuccia RC, Spear LP (2005) Sensitivity and tolerance to autonomic effects of ethanol in adolescent and adult rats during repeated vapor inhalation sessions. Alcohol Clin Exp Res 29:1809–1820PubMedCrossRefGoogle Scholar
  186. Roberts DC, Loh EA, Vickers G (1989) Self-administration of cocaine on a progressive ratio schedule in rats: dose–response relationship and effect of haloperidol pretreatment. Psychopharmacology (Berl) 97:535–538CrossRefGoogle Scholar
  187. Robins LN, Przybeck TR (1985) Age of onset of drug use as a factor in drug and other disorders. NIDA Res Monogr 56:178–192PubMedGoogle Scholar
  188. Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291PubMedCrossRefGoogle Scholar
  189. Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95(Suppl 2):S91–S117PubMedGoogle Scholar
  190. Robinson TE, Berridge KC (2001) Incentive-sensitization and addiction. Addiction 96:103–114PubMedCrossRefGoogle Scholar
  191. Robinson TE, Berridge KC (2008) Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R Soc Lond B Biol Sci 363:3137–3146PubMedCrossRefGoogle Scholar
  192. Robinson TE, Kolb B (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47(Suppl 1):33–46PubMedCrossRefGoogle Scholar
  193. Roesch MR, Takahashi Y, Gugsa N, Bissonette GB, Schoenbaum G (2007) Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude. J Neurosci 27:245–250PubMedCrossRefGoogle Scholar
  194. Russell JM, Newman SC, Bland RC (1994) Epidemiology of psychiatric disorders in Edmonton. Drug abuse and dependence. Acta Psychiatr Scand Suppl 376:54–62PubMedCrossRefGoogle Scholar
  195. SAMHSA (2008) National survey on drug use and health. SAMHSA, RockvilleGoogle Scholar
  196. Santucci AC, Capodilupo S, Bernstein J, Gomez-Ramirez M, Milefsky R, Mitchell H (2004) Cocaine in adolescent rats produces residual memory impairments that are reversible with time. Neurotoxicol Teratol 26:651–661PubMedCrossRefGoogle Scholar
  197. Schepis TS, Adinoff B, Rao U (2008) Neurobiological processes in adolescent addictive disorders. Am J Addict 17:6–23PubMedCrossRefGoogle Scholar
  198. Schneider M, Koch M (2003) Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology 28:1760–1769PubMedCrossRefGoogle Scholar
  199. Schochet TL, Kelley AE, Landry CF (2004) Differential behavioral effects of nicotine exposure in adolescent and adult rats. Psychopharmacology (Berl) 175:265–273CrossRefGoogle Scholar
  200. Schramm NL, Egli RE, Winder DG (2002) LTP in the mouse nucleus accumbens is developmentally regulated. Synapse 45:213–219PubMedCrossRefGoogle Scholar
  201. Schramm-Sapyta NL, Pratt AR, Winder DG (2004) Effects of periadolescent versus adult cocaine exposure on cocaine conditioned place preference and motor sensitization in mice. Psychopharmacology (Berl) 173:41–48CrossRefGoogle Scholar
  202. Schramm-Sapyta NL, Olsen CM, Winder DG (2005) Cocaine self-administration reduces excitatory responses in the mouse nucleus accumbens shell. Neuropsychopharmacology 31:1444–1451PubMedCrossRefGoogle Scholar
  203. Schramm-Sapyta NL, Morris RW, Kuhn CM (2006) Adolescent rats are protected from the conditioned aversive properties of cocaine and lithium chloride. Pharmacol Biochem Behav 84:344–352PubMedCrossRefGoogle Scholar
  204. Schramm-Sapyta NL, Cha YM, Chaudhry S, Wilson WA, Swartzwelder HS, Kuhn CM (2007) Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and adult rats. Psychopharmacology (Berl) 191:867–877CrossRefGoogle Scholar
  205. Schwandt ML, Barr CS, Suomi SJ, Higley JD (2007) Age-dependent variation in behavior following acute ethanol administration in male and female adolescent rhesus macaques (Macaca mulatta). Alcohol Clin Exp Res 31:228–237PubMedCrossRefGoogle Scholar
  206. Seeman P, Bzowej NH, Guan HC, Bergeron C, Becker LE, Reynolds GP, Bird ED, Riederer P, Jellinger K, Watanabe S et al (1987) Human brain dopamine receptors in children and aging adults. Synapse 1:399–404PubMedCrossRefGoogle Scholar
  207. Segal DS, Kuczenski R (1992a) In vivo microdialysis reveals a diminished amphetamine-induced DA response corresponding to behavioral sensitization produced by repeated amphetamine pretreatment. Brain Res 571:330–337PubMedCrossRefGoogle Scholar
  208. Segal DS, Kuczenski R (1992b) Repeated cocaine administration induces behavioral sensitization and corresponding decreased extracellular dopamine responses in caudate and accumbens. Brain Res 577:351–355PubMedCrossRefGoogle Scholar
  209. Sellers EM, Busto U, Kaplan HL (1989) Pharmacokinetic and pharmacodynamic drug interactions: implications for abuse liability testing. NIDA Res Monogr 92:287–306PubMedGoogle Scholar
  210. Shaffer HJ, Eber GB (2002) Temporal progression of cocaine dependence symptoms in the US National Comorbidity Survey. Addiction 97:543–554PubMedCrossRefGoogle Scholar
  211. Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20CrossRefGoogle Scholar
  212. Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42PubMedCrossRefGoogle Scholar
  213. Shram MJ, Funk D, Li Z, Le AD (2006) Periadolescent and adult rats respond differently in tests measuring the rewarding and aversive effects of nicotine. Psychopharmacology (Berl) 186:201–208CrossRefGoogle Scholar
  214. Shram MJ, Funk D, Li Z, Le AD (2007a) Acute nicotine enhances c-fos mRNA expression differentially in reward-related substrates of adolescent and adult rat brain. Neurosci Lett 418:286–291PubMedCrossRefGoogle Scholar
  215. Shram MJ, Funk D, Li Z, Le AD (2007b) Nicotine self-administration, extinction responding and reinstatement in adolescent and adult male rats: evidence against a biological vulnerability to nicotine addiction during adolescence. Neuropsychopharmacology 33:739–748PubMedCrossRefGoogle Scholar
  216. Shuster L, Webster GW, Yu G (1975a) Increased running response to morphine in morphine-pretreated mice. J Pharmacol Exp Ther 192:64–67PubMedGoogle Scholar
  217. Shuster L, Webster GW, Yu G (1975b) Perinatal narcotic addiction in mice: sensitization to morphine stimulation. Addict Dis 2:277–292PubMedGoogle Scholar
  218. Shuster L, Yu G, Bates A (1977) Sensitization to cocaine stimulation in mice. Psychopharmacology (Berl) 52:185–190CrossRefGoogle Scholar
  219. Shuster L, Hudson J, Anton M, Righi D (1982) Sensitization of mice to methylphenidate. Psychopharmacology (Berl) 77:31–36CrossRefGoogle Scholar
  220. Siegmund S, Vengeliene V, Singer MV, Spanagel R (2005) Influence of age at drinking onset on long-term ethanol self-administration with deprivation and stress phases. Alcohol Clin Exp Res 29:1139–1145PubMedCrossRefGoogle Scholar
  221. Sircar R, Sircar D (2005) Adolescent rats exposed to repeated ethanol treatment show lingering behavioral impairments. Alcohol Clin Exp Res 29:1402–1410PubMedCrossRefGoogle Scholar
  222. Slawecki CJ, Roth J, Gilder A (2006) Neurobehavioral profiles during the acute phase of ethanol withdrawal in adolescent and adult Sprague-Dawley rats. Behav Brain Res 170:41–51PubMedCrossRefGoogle Scholar
  223. Slotkin TA (2002) Nicotine and the adolescent brain: insights from an animal model. Neurotoxicol Teratol 24:369–384PubMedCrossRefGoogle Scholar
  224. Snyder KJ, Katovic NM, Spear LP (1998) Longevity of the expression of behavioral sensitization to cocaine in preweanling rats. Pharmacol Biochem Behav 60:909–914PubMedCrossRefGoogle Scholar
  225. Soderstrom K, Qin W, Williams H, Taylor DA, McMillen BA (2007) Nicotine increases FosB expression within a subset of reward- and memory-related brain regions during both peri- and post-adolescence. Psychopharmacology (Berl) 191:891–897CrossRefGoogle Scholar
  226. Soetens E, D’Hooge R, Hueting JE (1993) Amphetamine enhances human-memory consolidation. Neurosci Lett 161:9–12PubMedCrossRefGoogle Scholar
  227. Soetens E, Casaer S, D’Hooge R, Hueting JE (1995) Effect of amphetamine on long-term retention of verbal material. Psychopharmacology (Berl) 119:155–162CrossRefGoogle Scholar
  228. Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463PubMedCrossRefGoogle Scholar
  229. Spear LP, Brick J (1979) Cocaine-induced behavior in the developing rat. Behav Neural Biol 26:401–415PubMedCrossRefGoogle Scholar
  230. Spear LP, Horowitz GP, Lipovsky J (1982) Altered behavioral responsivity to morphine during the periadolescent period in rats. Behav Brain Res 4:279–288PubMedCrossRefGoogle Scholar
  231. Stevenson RA, Besheer J, Hodge CW (2008) Comparison of ethanol locomotor sensitization in adolescent and adult DBA/2J mice. Psychopharmacology (Berl) 197:361–370CrossRefGoogle Scholar
  232. Stinus L, Koob GF, Ling N, Bloom FE, Le Moal M (1980) Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate–dopamine interactions. Proc Natl Acad Sci U S A 77:2323–2327PubMedCrossRefGoogle Scholar
  233. Swartzwelder HS, Richardson RC, Markwiese-Foerch B, Wilson WA, Little PJ (1998) Developmental differences in the acquisition of tolerance to ethanol. Alcohol 15:311–314PubMedCrossRefGoogle Scholar
  234. Tambour S, Brown LL, Crabbe JC (2008) 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 32:2100–2106PubMedCrossRefGoogle Scholar
  235. Tarazi FI, Tomasini EC, Baldessarini RJ (1998a) Postnatal development of dopamine and serotonin transporters in rat caudate-putamen and nucleus accumbens septi. Neurosci Lett 254:21–24PubMedCrossRefGoogle Scholar
  236. Tarazi FI, Tomasini EC, Baldessarini RJ (1998b) Postnatal development of dopamine D4-like receptors in rat forebrain regions: comparison with D2-like receptors. Brain Res Dev Brain Res 110:227–233PubMedCrossRefGoogle Scholar
  237. Tarazi FI, Tomasini EC, Baldessarini RJ (1999) Postnatal development of dopamine D1-like receptors in rat cortical and striatolimbic brain regions: an autoradiographic study. Dev Neurosci 21:43–49PubMedCrossRefGoogle Scholar
  238. Tarter R, Vanyukov M, Giancola P, Dawes M, Blackson T, Mezzich A, Clark DB (1999) Etiology of early age onset substance use disorder: a maturational perspective. Dev Psychopathol 11:657–683PubMedCrossRefGoogle Scholar
  239. Teicher MH, Andersen SL, Hostetter JC Jr (1995) Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens. Brain Res Dev Brain Res 89:167–172PubMedCrossRefGoogle Scholar
  240. Teichner G, Horner MD, Harvey RT (2001) Neuropsychological predictors of the attainment of treatment objectives in substance abuse patients. Int J Neurosci 106:253–263PubMedCrossRefGoogle Scholar
  241. Terry AV Jr, Hernandez CM, Hohnadel EJ, Bouchard KP, Buccafusco JJ (2005) Cotinine, a neuroactive metabolite of nicotine: potential for treating disorders of impaired cognition. CNS Drug Rev 11:229–252PubMedGoogle Scholar
  242. Thomas MJ, Beurrier C, Bonci A, Malenka RC (2001) Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci 4:1217–1223PubMedCrossRefGoogle Scholar
  243. Tirelli E, Laviola G, Adriani W (2003) Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents. Neurosci Biobehav Rev 27:163–178PubMedCrossRefGoogle Scholar
  244. Torrella TA, Badanich KA, Philpot RM, Kirstein CL, Wecker L (2004) Developmental differences in nicotine place conditioning. Ann N Y Acad Sci 1021:399–403PubMedCrossRefGoogle Scholar
  245. Torres OV, Tejeda HA, Natividad LA, O’Dell LE (2008) Enhanced vulnerability to the rewarding effects of nicotine during the adolescent period of development. Pharmacol Biochem Behav 90:658–663PubMedCrossRefGoogle Scholar
  246. Truxell EM, Molina JC, Spear NE (2007) Ethanol intake in the juvenile, adolescent, and adult rat: effects of age and prior exposure to ethanol. Alcohol Clin Exp Res 31:755–765PubMedCrossRefGoogle Scholar
  247. Ujike H, Tsuchida K, Akiyama K, Fujiwara Y, Kuroda S (1995) Ontogeny of behavioral sensitization to cocaine. Pharmacol Biochem Behav 50:613–617PubMedCrossRefGoogle Scholar
  248. Vaidya JG, Grippo AJ, Johnson AK, Watson D (2004) A comparative developmental study of impulsivity in rats and humans: the role of reward sensitivity. Ann N Y Acad Sci 1021:395–398PubMedCrossRefGoogle Scholar
  249. Vanderschuren LJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019PubMedCrossRefGoogle Scholar
  250. Varlinskaya EI, Spear LP (2004a) Acute ethanol withdrawal (hangover) and social behavior in adolescent and adult male and female Sprague-Dawley rats. Alcohol Clin Exp Res 28:40–50PubMedCrossRefGoogle Scholar
  251. Varlinskaya EI, Spear LP (2004b) Changes in sensitivity to ethanol-induced social facilitation and social inhibition from early to late adolescence. Ann N Y Acad Sci 1021:459–461PubMedCrossRefGoogle Scholar
  252. Varlinskaya EI, Spear LP (2006) Ontogeny of acute tolerance to ethanol-induced social inhibition in Sprague-Dawley rats. Alcohol Clin Exp Res 30:1833–1844PubMedCrossRefGoogle Scholar
  253. Vastola BJ, Douglas LA, Varlinskaya EI, Spear LP (2002) Nicotine-induced conditioned place preference in adolescent and adult rats. Physiol Behav 77:107–114PubMedCrossRefGoogle Scholar
  254. Vetter CS, Doremus-Fitzwater TL, Spear LP (2007) Time course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions. Alcohol Clin Exp Res 31:1159–1168PubMedCrossRefGoogle Scholar
  255. Vezina P, Leyton M (2009) Conditioned cues and the expression of stimulant sensitization in animals and humans. Neuropharmacology 56(Suppl 1):160–168PubMedCrossRefGoogle Scholar
  256. Volkow ND, Fowler JS (2000) Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex 10:318–325PubMedCrossRefGoogle Scholar
  257. Volkow ND, Fowler JS, Wang GJ, Swanson JM, Telang F (2007) Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch Neurol 64:1575–1579PubMedCrossRefGoogle Scholar
  258. Vorhees CV, Reed TM, Morford LL, Fukumura M, Wood SL, Brown CA, Skelton MR, McCrea AE, Rock SL, Williams MT (2005) Periadolescent rats (P41–50) exhibit increased susceptibility to d-methamphetamine-induced long-term spatial and sequential learning deficits compared to juvenile (P21–30 or P31–40) or adult rats (P51–60). Neurotoxicol Teratol 27:117–134PubMedCrossRefGoogle Scholar
  259. Walker QD, Kuhn CM (2008) Cocaine increases stimulated dopamine release more in periadolescent than adult rats. Neurotoxicol Teratol 30:412–418PubMedCrossRefGoogle Scholar
  260. Welzl H, D’Adamo P, Lipp HP (2001) Conditioned taste aversion as a learning and memory paradigm. Behav Brain Res 125:205–213PubMedCrossRefGoogle Scholar
  261. Wenger GR, Wright DW (1990) Behavioral effects of cocaine and its interaction with d-amphetamine and morphine in rats. Pharmacol Biochem Behav 35:595–600PubMedCrossRefGoogle Scholar
  262. White AM, Swartzwelder HS (2005) Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults. Recent Dev Alcohol 17:161–176PubMedCrossRefGoogle Scholar
  263. White AM, Ghia AJ, Levin ED, Swartzwelder HS (2000) Binge pattern ethanol exposure in adolescent and adult rats: differential impact on subsequent responsiveness to ethanol. Alcohol Clin Exp Res 24:1251–1256PubMedCrossRefGoogle Scholar
  264. Wilhelm CJ, Mitchell SH (2008) Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes. Genes Brain Behav 7:705–713PubMedCrossRefGoogle Scholar
  265. Wilhelm CJ, Reeves JM, Phillips TJ, Mitchell SH (2007) Mouse lines selected for alcohol consumption differ on certain measures of impulsivity. Alcohol Clin Exp Res 31:1839–1845PubMedCrossRefGoogle Scholar
  266. Wilmouth CE, Spear LP (2004) Adolescent and adult rats’ aversion to flavors previously paired with nicotine. Ann N Y Acad Sci 1021:462–464PubMedCrossRefGoogle Scholar
  267. Wilmouth CE, Spear LP (2006) Withdrawal from chronic nicotine in adolescent and adult rats. Pharmacol Biochem Behav 85:648–657PubMedCrossRefGoogle Scholar
  268. Winder DG, Egli RE, Schramm NL, Matthews RT (2002) Synaptic plasticity in drug reward circuitry. Curr Mol Med 2:667–676PubMedCrossRefGoogle Scholar
  269. Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263PubMedCrossRefGoogle Scholar
  270. Wise RA, Yokel RA, DeWit H (1976) Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats. Science 191:1273–1275PubMedCrossRefGoogle Scholar
  271. Yuferov V, Nielsen D, Butelman E, Kreek MJ (2005) Microarray studies of psychostimulant-induced changes in gene expression. Addict Biol 10:101–118PubMedCrossRefGoogle Scholar
  272. Zakharova E, Leoni G, Kichko I, Izenwasser S (2008a) Differential effects of methamphetamine and cocaine on conditioned place preference and locomotor activity in adult and adolescent male rats. Behav Brain Res 198:45–50PubMedCrossRefGoogle Scholar
  273. Zakharova E, Wade D, Izenwasser S (2008b) Sensitivity to cocaine conditioned reward depends on sex and age. Pharmacol Biochem Behav 92:131–134PubMedCrossRefGoogle Scholar
  274. Zhang Y, Picetti R, Butelman ER, Schlussman SD, Ho A, Kreek MJ (2008) Behavioral and neurochemical changes induced by oxycodone differ between adolescent and adult mice. Neuropsychopharmacology 34:912–922PubMedCrossRefGoogle Scholar
  275. Zombeck JA, Gupta T, Rhodes JS (2009) Evaluation of a pharmacokinetic hypothesis for reduced locomotor stimulation from methamphetamine and cocaine in adolescent versus adult male C57BL/6J mice. Psychopharmacology (Berl) 201:589–599CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Nicole L. Schramm-Sapyta
    • 1
  • Q. David Walker
    • 1
  • Joseph M. Caster
    • 1
  • Edward D. Levin
    • 1
  • Cynthia M. Kuhn
    • 1
  1. 1.Duke UniversityDurhamUSA

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