Skip to main content

Advertisement

Log in

Higher long-lasting ethanol sensitization after adolescent ethanol exposure in mice

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is a possible consequence of ethanol exposure during adolescence.

Objectives

The aim of this study was to characterize the long-term alterations in the stimulant effects of ethanol and in the rate of ethanol sensitization in mice pre-exposed to ethanol during adolescence in comparison to mice pre-exposed to ethanol in adulthood.

Methods

Adolescent and adult female Swiss mice were injected with saline or ethanol (2.5 or 4 g/kg) during 14 consecutive days. After a 3-week period of ethanol abstinence, mice were tested as adults before and after a second exposure to daily repeated ethanol injections.

Results

All mice pre-exposed to ethanol as adults or adolescents showed higher stimulant effects when re-exposed to ethanol 3 weeks later. However, this enhanced sensitivity to the stimulant effects of ethanol was of significantly higher magnitude in mice repeatedly injected with high ethanol doses (4 g/kg) during adolescence. Furthermore, the increased expression of ethanol stimulant effects in these mice was maintained even after a second procedure of ethanol sensitization.

Conclusions

Adolescence is a critical period for the development of a sensitization to ethanol stimulant properties providing that high intermittent ethanol doses are administered. These results might contribute to explain the relationship between age at first alcohol use and risks of later alcohol problems and highlight the dangers of repeated consumption of high alcohol amounts in young adolescents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Agabio R, Carai MA, Lobina C, Pani M, Reali R, Vacca G, Gessa GL, Colombo G (2001) Alcohol stimulates motor activity in selectively bred Sardinian alcohol-preferring (sP), but not in Sardinian alcohol-nonpreferring (sNP), rats. Alcohol 23:123–126

    Article  PubMed  CAS  Google Scholar 

  • Badanich KA, Maldonado AM, Kirstein CL (2007) Chronic ethanol exposure during adolescence increases basal dopamine in the nucleus accumbens septi during adulthood. Alcohol Clin Exp Res 31:895–900

    Article  PubMed  CAS  Google Scholar 

  • Bates ME, Labouvie EW (1995) Adolescent risk factors and the prediction of persistent alcohol and drug use into adulthood. Alcohol Clin Exp Res 21:944–950

    Article  Google Scholar 

  • Bergstrom HC, McDonald CG, Smith RF (2006) Alcohol exposure during adolescence impairs auditory fear conditioning in adult Long-Evans rats. Physiol Behav 88:466–472

    Article  PubMed  CAS  Google Scholar 

  • Blizard DA, Vandenbergh DJ, Jefferson AL, Chatlos CD, Vogler GP, McClearn GE (2004) Effects of periadolescent ethanol exposure on alcohol preference in two BALB substrains. Alcohol 34:177–185

    Article  PubMed  CAS  Google Scholar 

  • Brunell CS, 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 29:1641–1653

    Article  PubMed  Google Scholar 

  • Camarini R, Hodge CW (2004) Ethanol preexposure increases ethanol self-administration in C57BL/6J and DBA/2J mice. Pharmacol Biochem Behav 79:623–632

    Article  PubMed  CAS  Google Scholar 

  • Chambers RA, Taylor JR, Potenza MN (2003) Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 160:1041–1052

    Article  PubMed Central  PubMed  Google Scholar 

  • Coleman LG Jr, He J, Lee J, Styner M, Crews FT (2011) Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice. Alcohol Clin Exp Res 35:671–688

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Colombo G, Agabio R, Lobina C, Reali R, Vacca G, Gessa GL (1998) Stimulation of locomotor activity by voluntarily consumed ethanol in Sardinian alcohol-preferring rats. Eur J Pharmacol 357:109–113

    Article  PubMed  CAS  Google Scholar 

  • Crews F, He J, Hodge C (2007) Adolescent cortical development: a critical period of vulnerability for addiction. Pharmacol Biochem Behav 86:189–199

    Article  PubMed  CAS  Google Scholar 

  • DeWit DJ, Adlaf EM, Offord DR, Ogborne AC (2000) Age at first alcohol use: a risk factor for the development of alcohol disorders. Am J Psychiatry 157:745–750

    Article  PubMed  CAS  Google Scholar 

  • Diaz-Granados JL, Graham DL (2007) The effects of continuous and intermittent ethanol exposure in adolescence on the aversive properties of ethanol during adulthood. Alcohol Clin Exp Res 31:2020–2027

    Article  PubMed  Google Scholar 

  • Didone V, Quoilin C, Tirelli E, Quertemont E (2008) Parametric analysis of the development and expression of ethanol-induced behavioral sensitization in female Swiss mice: effects of dose, injection schedule, and test context. Psychopharmacology 201:249–260

    Article  PubMed  CAS  Google Scholar 

  • Doremus-Fitzwater TL, Varlinskaya EI, Spear LP (2010) Motivational systems in adolescence: possible implications for age differences in substance abuse and other risk-taking behaviors. Brain Cogn 72:114–123

    Article  PubMed Central  PubMed  Google Scholar 

  • Ernst M, Romeo RD, Andersen SL (2009) Neurobiology of the development of motivated behaviors in adolescence: a window into a neural systems model. Pharmacol Biochem 93:199–211

    Article  CAS  Google Scholar 

  • Graham DL, Diaz-Granados JL (2006) Periadolescent exposure to ethanol and diazepam alters the aversive properties of ethanol in adult mice. Pharmacol Biochem Behav 84:406–414

    Article  PubMed  CAS  Google Scholar 

  • Grant BF, Dawson DA (1997) Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. J Subst Abuse 9:103–110

    Article  PubMed  CAS  Google Scholar 

  • Insel TR, Miller LP, Gelhard RE (1990) The ontogeny of excitatory amino acid receptors in rat forebrain—I. N-Methyl-d-aspartate and quisqualate receptors. Neuroscience 35:31–43

    Article  PubMed  CAS  Google Scholar 

  • King AC, Houle T, de Wit H, Holdstock L, Schuster A (2002) Biphasic alcohol response differs in heavy versus light drinkers. Alcohol Clin Exp Res 26:827–835

    Article  PubMed  CAS  Google Scholar 

  • Laurie DJ, Wisden W, Seeburg PH (1992) The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain III Embryonic and postnatal development. J Neurosci 12:4151–4172

    PubMed  CAS  Google Scholar 

  • Laviola G, Macrì S, Morley-Fletcher S, Adriani W (2003) Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence. Neurosci Biobehav Rev 27:19–31

    Article  PubMed  Google Scholar 

  • Lessov CN, Phillips TJ (1998) Duration of sensitization to the locomotor stimulant effects of ethanol in mice. Psychopharmacol (Berl) 135:374–382

    Article  CAS  Google Scholar 

  • Lessov CN, Palmer AA, Quick EA, Phillips TJ (2001a) Voluntary ethanol drinking in C57BL/6J and DBA/2J mice before and after sensitization to the locomotor stimulant effects of ethanol. Psychopharmacology 155:91–99

    Article  PubMed  CAS  Google Scholar 

  • Lessov CN, Risinger FO, Phillips TJ (2001b) Attenuation of ethanol-induced conditioned taste aversion in mice sensitized to the locomotor stimulant effects of ethanol. Behav Neurosci 115:146–153

    Article  PubMed  CAS  Google Scholar 

  • Maldonado AM, Finkbeiner LM, Alipour KK, Kirstein CL (2008) Voluntary ethanol consumption differs in adolescent and adult male rats using a modified sucrose-fading paradigm. Alcohol Clin Exp Res 32:1574–1582

    Article  PubMed  CAS  Google Scholar 

  • Maldonado-Devincci AM, Alipour KK, Michael LA, Kirstein CL (2010a) Repeated binge ethanol administration during adolescence enhances voluntary sweetened ethanol intake in young adulthood in male and female rats. Pharmacol Biochem Behav 96:476–487

    Article  PubMed  CAS  Google Scholar 

  • Maldonado-Devincci AM, Badanich KA, Kirstein CL (2010b) Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry. Alcohol 44:57–66

    Article  PubMed  CAS  Google Scholar 

  • Martin CA, Kelly TH, Rayens MK, Brogli BR, Brenzel A, Smith WJ et al (2002) Sensation seeking, puberty, and nicotine, alcohol, and marijuana use in adolescence. J Am Acad Child Adolesc Psychiatry 41:1495–1502

    Article  PubMed  Google Scholar 

  • Matthews DB, Tinsley KL, Diaz-Granados JL, Tokunaga S, Silvers JM (2008) Chronic intermittent exposure to ethanol during adolescence produces tolerance to the hypnotic effects of ethanol in male rats: a dose-dependent analysis. Alcohol 42:617–621

    Article  PubMed  CAS  Google Scholar 

  • McBride WJ, Bell RL, Rodd ZA, Strother WN, Murphy JM (2005) Adolescent alcohol drinking and its long-range consequences. Studies with animal models. Recent Dev Alcohol 17:123–142

    Article  PubMed  Google Scholar 

  • Melón LC, Boehm SL 2nd (2011) Role of genotype in the development of locomotor sensitization to alcohol in adult and adolescent mice: comparison of the DBA/2J and C57BL/6J inbred mouse strains. Alcohol Clin Exp Res 35:1351–1360

    Article  PubMed Central  PubMed  Google Scholar 

  • Miller JW, Naimi TS, Brewer RD, Jones SE (2007) Binge drinking and associated health risk behaviors among high school students. Pediatrics 119:76–85

    Article  PubMed  Google Scholar 

  • Nelson DE, Naimi TS, Brewer RD, Nelson HA (2009) State alcohol-use estimates among youth and adults, 1993–2005. Am J Prev Med 36:218–224

    Article  PubMed  Google Scholar 

  • Pascual M, Blanco AM, Cauli O, Miñarro J, Guerri C (2007) Intermittent ethanol exposure induces inflammatory brain damage and causes long-term behavioural alterations in adolescent rats. Eur J Neurosci 25:541–550

    Article  PubMed  Google Scholar 

  • Pascual M, Boix J, Felipo V, Guerri C (2009) 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

    Article  PubMed  CAS  Google Scholar 

  • Quoilin C, Didone V, Tirelli E, Quertemont E (2012a) Chronic ethanol exposure during adolescence alters the behavioral responsiveness to ethanol in adult mice. Behav Brain Res 229:1–9

    Article  PubMed  CAS  Google Scholar 

  • Quoilin C, Didone V, Tirelli E, Quertemont E (2012b) Developmental differences in ethanol-induced sensitization using postweanling, adolescent, and adult Swiss mice. Psychopharmacology 219:1165–1177

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro AF, Pigatto G, Goeldner FO, Lopes JF, de Lacerda RB (2008) Lack of relation between drug-seeking behavior in an addiction model and the expression of behavioral sensitization in response to ethanol challenge in mice. J Neural Trans 115:43–54

    Article  CAS  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2008) Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R Soc Lond B Biol Sci 363:3137–3146

    Article  PubMed Central  PubMed  Google Scholar 

  • Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li TK (2002a) 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

    Article  PubMed  CAS  Google Scholar 

  • Rodd-Henricks ZA, Bell RL, Kuc KA, Murphy JM, McBride WJ, Lumeng L, Li TK (2002b) 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

    Article  PubMed  CAS  Google Scholar 

  • Sahr AE, Thielen RJ, Lumeng L, Li TK, McBride WJ (2004) Long-lasting alterations of the mesolimbic dopamine system after periadolescent ethanol drinking by alcohol-preferring rats. Alcohol Clin Exp Res 28:702–711

    Article  PubMed  CAS  Google Scholar 

  • Silvers JM, Tokunaga S, Mittleman G, Matthews DB (2003) Chronic intermittent injections of high-dose ethanol during adolescence produce metabolic, hypnotic, and cognitive tolerance in rats. Alcohol Clin Exp Res 27:1606–1612

    Article  PubMed  CAS  Google Scholar 

  • Sircar R, Sircar D (2005) Adolescent rats exposed to repeated ethanol treatment show lingering behavioral impairments. Alcohol Clin Exp Res 29:1402–1410

    Article  PubMed  Google Scholar 

  • Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463

    Article  PubMed  CAS  Google Scholar 

  • Stevenson RA, Besheer J, Hodge CW (2008) Comparison of ethanol locomotor sensitization in adolescent and adult DBA/2J mice. Psychopharmacol (Berl) 197:361–370

    Article  CAS  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2010) Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of national findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10–4586 Findings). U.S. Department of Health and Human Services, Rockville

    Google Scholar 

  • Tambour S, Didone V, Tirelli E, Quertemont E (2006) Locomotor effects of ethanol and acetaldehyde after peripheral and intraventricular injections in Swiss and C57BL/6J mice. Behav Brain Res 172:145–154

    Article  PubMed  CAS  Google Scholar 

  • Tirelli E, Laviola G, Adriani W (2003) Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents. Neurosci Biobehav Rev 27:163–178

    Google Scholar 

  • 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 31:1159–1168

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • 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 24:1251–1256

    Article  PubMed  CAS  Google Scholar 

  • White AM, Bae JG, Truesdale MC, Ahmad S, Wilson WA, Swartzwelder HS (2002) Chronic-intermittent ethanol exposure during adolescence prevents normal developmental changes in sensitivity to ethanol-induced motor impairments. Alcohol Clin Exp Res 26:960–968

    Article  PubMed  CAS  Google Scholar 

  • Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492

    Article  PubMed  CAS  Google Scholar 

  • Xia Y, Haddad GG (1992) Ontogeny and distribution of GABAA receptors in rat brainstem and rostral brain regions. Neuroscience 49:973–989

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Fonds National de la Recherche Scientifique (FNRS) and the Fonds Spéciaux pour la Recherche de l'Université de Liège obtained by Etienne Quertemont. Caroline Quoilin is a research assistant under contract with the FNRS.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Etienne Quertemont.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quoilin, C., Didone, V., Tirelli, E. et al. Higher long-lasting ethanol sensitization after adolescent ethanol exposure in mice. Psychopharmacology 231, 1821–1829 (2014). https://doi.org/10.1007/s00213-013-3376-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3376-2

Keywords

Navigation