Skip to main content

Advertisement

SpringerLink
Log in

Developmental differences in ethanol-induced sensitization using postweanling, adolescent, and adult Swiss mice

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

Abstract

Rationale

The maturing adolescent brain has been suggested to be more sensitive than the adult brain to ethanol-induced neuroadaptations. In animal studies, sensitization to the stimulant effects of ethanol is used to study the vulnerability to chronic ethanol-induced neurobehavioral alterations.

Objectives

The aim of the present study was to systematically characterize age-dependent changes in the development and expression of the sensitization to the stimulant effects of a range of ethanol doses in female Swiss mice. Three ages were studied: 21-day-old mice (postweanlings), 35-day-old mice (adolescents), and 63-day-old mice (adults).

Methods

Postweanling, adolescent, and adult mice were daily injected with saline or various ethanol doses (1.5 to 4 g/kg) for 7 days. They were then tested for acute and sensitized locomotor activity.

Results

Postweanling and adolescent mice were more sensitive than adult mice to the acute stimulant effects of ethanol. In adult mice, daily injections of ethanol at doses between 2.5 and 4 g/kg led to significant sensitization. Higher ethanol doses (3.5 and 4 g/kg) were required to induce sensitization in postweanling and adolescent mice. However, younger mice showed ethanol sensitization of higher magnitude.

Conclusions

Young mice develop very strong ethanol sensitization at doses that mimic binge drinking in humans. These results might explain why early ethanol drinking during adolescence is related to a higher prevalence of subsequent alcohol disorders.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Acevedo MB, Molina JC, Nizhnikov ME, Spear NE, Pautassi RM (2010) High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence. Dev Psychobiol 52:424–440

    Article  PubMed  CAS  Google Scholar 

  • Adriani W, Chiarotti F, Laviola G (1998) Elevated novelty seeking and peculiar d-amphetamine sensitization in periadolescent mice compared with adult mice. Behav Neurosci 112:1152–1166

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Arnett J (1992) Reckless behavior in adolescence: a developmental perspective. Dev Rev 12:339–373

    Article  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 

  • Bell RL, Rodd ZA, Lumeng L, Murphy JM, McBride WJ (2006a) The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict Biol 11:270–288

    Article  PubMed  Google Scholar 

  • Bell RL, Rodd ZA, Sable HJ, Schultz JA, Hsu CC, Lumeng L, Murphy JM, McBride WJ (2006b) Daily patterns of ethanol drinking in peri-adolescent and adult alcohol-preferring (P) rats. Pharmacol Biochem Behav 83:35–46

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, Taylor JB, Cunningham MC (2000) Convergence and plasticity of monoaminergic systems in the medial prefrontal cortex during the postnatal period: implications for the development of psychopathology. Cereb Cortex 10:1014–1027

    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 

  • Branchi I (2009) The mouse communal nest: investigating the epigenetic influences of the early social environment on brain and behavior development. Neurosci Biobehav Rev 4:551–559

    Article  Google Scholar 

  • Broadbent J, Kampmueller KM, Koonse SA (2003) Expression of behavioral sensitization to ethanol by DBA/2J mice: the role of NMDA and non-NMDA glutamate receptors. Psychopharmacology (Berl) 167:225–234

    CAS  Google Scholar 

  • Broadbent J, Kampmueller KM, Koonse SA (2005) Role of dopamine in behavioral sensitization to ethanol in DBA/2J mice. Alcohol 35:137–148

    Article  PubMed  CAS  Google Scholar 

  • Brodie MS (2002) Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin Exp Res 26:1024–1030

    Article  PubMed  CAS  Google Scholar 

  • Brodie MS, Shefner SA, Dunwiddie TV (1990) Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 29:65–69

    Article  Google Scholar 

  • 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 1193:34–42

    Article  PubMed  CAS  Google Scholar 

  • Camarini R, Pautassi RM, Méndez M, Quadros IM, Souza-Formigoni ML, Boerngen-Lacerda R (2010) Behavioral and neurochemical studies in distinct animal models of ethanol's motivational effects. Curr Drug Abuse Rev 3:205–221

    Article  PubMed  CAS  Google Scholar 

  • Camarini R, Marcourakis T, Teodorov E, Yonamine M, Calil HM (2011) Ethanol-induced sensitization depends preferentially on D1 rather than D2 dopamine receptors. Pharmacol Biochem Behav 98:173–180

    Article  PubMed  CAS  Google Scholar 

  • Carrara-Nascimento PF, Griffin WC 3rd, Pastrello DM, Olive MF, Camarini R (2011) Changes in extracellular levels of glutamate in the nucleus accumbens after ethanol-induced behavioral sensitization in adolescent and adult mice. Alcohol 45:451–460

    Article  PubMed  CAS  Google Scholar 

  • Cha YM, Li Q, Wilson WA, Swartzwelder HS (2006) Sedative and GABAergic effects of ethanol on male and female rats. Alcohol Clin Exp Res 30:113–118

    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  Google Scholar 

  • Collins SL, Izenwasser S (2002) Cocaine differentially alters behavior and neurochemistry in periadolescent versus adult rats. Brain Res Dev Brain Res 138:27–34

    Article  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 

  • Csikszentmihalyi M, Larson R, Prescott S (1977) The ecology of adolescent activity and experience. J Youth Adolesc 6:281–294

    Article  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 

  • 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 (Berl) 201:249–260

    Article  CAS  Google Scholar 

  • Ding ZM, Rodd ZA, Engleman EA, McBride WJ (2009) Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol. Alcohol Clin Exp Res 33:1571–1581

    Article  PubMed  CAS  Google Scholar 

  • Doremus TL, Brunell SC, Rajendran P, Spear LP (2005) Factors influencing elevated ethanol consumption in adolescent relative to adult rats. Alcohol Clin Exp Res 29:1796–1808

    Article  PubMed  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  Google Scholar 

  • Faria RR, Lima Rueda AV, Sayuri C, Soares SL, Malta MB, Carrara-Nascimento PF, da Silva AA, Marcourakis T, Yonamine M, Scavone C, Giorgetti Britto LR, Camarini R (2008) Environmental modulation of ethanol-induced locomotor activity: correlation with neuronal activity in distinct brain regions of adolescent and adult Swiss mice. Brain Res 1239:127–140

    Article  PubMed  CAS  Google Scholar 

  • Frantz KJ, O'Dell LE, Parsons LH (2007) Behavioral and neurochemical responses to cocaine in periadolescent and adult rats. Neuropsychopharmacology 32:625–637

    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 

  • Hefner K, Holmes A (2007) An investigation of the behavioral actions of ethanol across adolescence in mice. Psychopharmacology (Berl) 191:311–322

    Article  CAS  Google Scholar 

  • King TS, Chinchilli VM (2001) Robust estimators of the concordance correlation coefficient. J Biopharm Stat 11:83–105

    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 

  • Kolta MG, Scalzo FM, Ali SF, Holson RR (1990) Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats. Psychopharmacology (Berl) 100:377–382

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Little PJ, Kuhn CM, Wilson WA, Swartzwelder HS (1996) Differential effects of ethanol in adolescent and adult rats. Alcohol Clin Exp Res 20:1346–1351

    Article  PubMed  CAS  Google Scholar 

  • Moore EM, Mariani JN, Linsenbardt DN, Melón LC, Boehm SL 2nd (2010) Adolescent C57BL/6J (but not DBA/2J) mice consume greater amounts of limited-access ethanol compared to adults and display continued elevated ethanol intake into adulthood. Alcohol Clin Exp Res 34:734–742

    Article  PubMed  Google Scholar 

  • Niculescu M, Ehrlich ME, Unterwald EM (2005) Age-specific behavioral responses to psychostimulants in mice. Pharmacol Biochem Behav 82:280–288

    Article  PubMed  CAS  Google Scholar 

  • Phillips TJ, Roberts AJ, Lessov CN (1997) Behavioral sensitization to ethanol: genetics and the effects of stress. Pharmacol Biochem Behav 57:487–493

    Article  PubMed  CAS  Google Scholar 

  • Primus RJ, Kellogg CK (1989) Pubertal-related changes influence the development of environment-related social interaction in the male rat. Dev Psychobiol 22:633–643

    Article  PubMed  CAS  Google Scholar 

  • Quoilin C, Didone V, Tirelli E, Quertemont E (2010) Ontogeny of the stimulant and sedative effects of ethanol in male and female Swiss mice: gradual changes from weaning to adulthood. Psychopharmacology (Berl) 212:501–512

    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 (2001) Incentive–sensitization and addiction. Addiction 96:103–114

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53

    Article  PubMed  Google Scholar 

  • Rodd ZA, Bell RL, McKinzie DL, Webster AA, Murphy JM, Lumeng L, Li TK, McBride WJ (2004) Low-dose stimulatory effects of ethanol during adolescence in rat lines selectively bred for high alcohol intake. Alcohol Clin Exp Res 28:535–543

    Article  PubMed  CAS  Google Scholar 

  • Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ (2005a) Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res 29:358–366

    Article  PubMed  CAS  Google Scholar 

  • Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ (2005b) Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation. J Pharmacol Exp Ther 315:648–657

    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 

  • Schöberl S, Nickel P, Schmutzer G, Siekmeyer W, Kiess W (2008) Acute ethanol intoxication among children and adolescents. A retrospective analysis of 173 patients admitted to a university children hospital. Klin Padiatr 220:253–258

    Article  PubMed  Google Scholar 

  • Schuckit MA, Smith TL, Kalmijn J, Tsuang J, Hesselbrock V, Bucholz K (2000) Response to alcohol in daughters of alcoholics: a pilot study and a comparison with sons of alcoholics. Alcohol Alcohol 35:242–248

    PubMed  CAS  Google Scholar 

  • Silveri MM, Spear LP (1998) Decreased sensitivity to the hypnotic effects of ethanol early in ontogeny. Alcohol Clin Exp Res 22:670–676

    Article  PubMed  CAS  Google Scholar 

  • Silveri MM, Spear LP (2000) Ontogeny of ethanol elimination and ethanol-induced hypothermia. Alcohol 20:45–53

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Stanwood GD, McElligot S, Lu L, McGonigle P (1997) Ontogeny of dopamine D3 receptors in the nucleus accumbens of the rat. Neurosci Lett 233:13–16

    Article  Google Scholar 

  • Stevenson RA, Besheer J, Hodge CW (2008) Comparison of ethanol locomotor sensitization in adolescent and adult DBA/2J mice. Psychopharmacology (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). US Department of Health and Human Services, Rockville

  • Tarazi FI, Baldessarini RJ (2000) Comparative postnatal development of dopamine D(1), D(2) and D(4) receptors in rat forebrain. Inter J Dev Neurosci 18:29–37

    Article  CAS  Google Scholar 

  • Tarazi FI, Tomasini EC, Baldessarini RJ (1998) Postnatal development of dopamine and serotonin transporters in rat caudate-putamen and nucleus accumbens septi. Neurosci Lett 254:21–24

    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

    Article  PubMed  Google Scholar 

  • 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 31:755–765

    Article  PubMed  CAS  Google Scholar 

  • Vanderschuren LJ, Kalivas PW (2000) Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl) 151:99–120

    Article  CAS  Google Scholar 

  • Vanderschuren LJMJ, Pierce RC (2010) Sensitization processes in drug addiction. Curr Top Behav Neurosci 3:179–195

    Article  PubMed  Google Scholar 

  • Varlinskaya EI, Spear LP (2002) Acute effects of ethanol on social behavior of adolescent and adult rats: role of familiarity of the test situation. Alcohol Clin Exp Res 26:1502–1511

    Article  PubMed  Google Scholar 

  • White AM, Truesdale MC, Bae JG, Ahmad S, Wilson WA, Best PJ, Swartzwelder HS (2002) Differential effects of ethanol on motor coordination in adolescent and adult rats. Pharmacol Biochem Behav 73:673–677

    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 

Download references

Acknowledgements

This work was supported by grants from Fonds National de la Recherche Scientifique (FNRS) and 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

  1. Centre de Neurosciences Cognitives et Comportementales, Université de Liège, Boulevard du Rectorat 5/B32, Liège, Belgium

    Caroline Quoilin, Vincent Didone, Ezio Tirelli & Etienne Quertemont

Authors
  1. Caroline Quoilin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Didone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ezio Tirelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Etienne Quertemont
    View author publications

    You can also search for this author in PubMed Google Scholar

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. Developmental differences in ethanol-induced sensitization using postweanling, adolescent, and adult Swiss mice. Psychopharmacology 219, 1165–1177 (2012). https://doi.org/10.1007/s00213-011-2453-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2453-7

Keywords

Search

Navigation