[en] Rationale: The adolescent period is characterized by a specific sensitivity to the effects of alcohol, which is believed to contribute to the enhanced risks of alcohol dependence when drinking is initiated early during adolescence. In adolescent rodents, while the reduced sensitivity to the sedative effects of ethanol has been well characterized, its stimulant effects have not yet been extensively studied. Objectives: The present study characterized the development of the stimulant and sedative effects of acute ethanol in male and female Swiss mice from weaning to early adulthood and tested whether both effects are interrelated. Methods: In a first experiment, mice aged 21, 28, 35, 42 and 60 days were injected with various ethanol doses and tested for ethanol-induced locomotor activity. In an independent experiment, mice of the same groups of age were injected with 4 g/kg ethanol and ethanol-induced sedation was quantified with the loss of righting reflex procedure. Results: In male and female mice, the stimulant effects of ethanol gradually decreased, whereas its sedative effects increased with age. When the sedation was statistically controlled using a covariance analysis, the differences between adult and juvenile mice in the locomotor stimulation were significantly reduced. Conclusions: From weaning to early adulthood, the acute stimulant and sedative effects of ethanol show gradual changes that are similar in male and female mice. Although the initial tolerance to the sedative effects of ethanol contribute to the changes in ethanol-induced locomotor activity, young mice also show a higher sensitivity to the stimulant effects of ethanol.
Research center :
Centre de Neurosciences Cognitives et Comportementales - ULiège
Disciplines :
Neurosciences & behavior
Author, co-author :
Quoilin, Caroline ; Université de Liège - ULiège > Département des sciences cognitives > Psychologie quantitative
Didone, Vincent ; Université de Liège - ULiège > Département des sciences cognitives > Psychologie quantitative
Tirelli, Ezio ; Université de Liège - ULiège > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér.
Quertemont, Etienne ; Université de Liège - ULiège > Département des sciences cognitives > Psychologie quantitative
Language :
English
Title :
Ontogeny of the stimulant and sedative effects of ethanol in male and female Swiss mice: gradual changes from weaning to adulthood
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
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 83:35-46
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
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
Boehm SL 2nd, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, Blednov YA, Harris RA (2004) gamma- Aminobutyric acid A receptor subunit mutant mice: New perspectives on alcohol actions. Biochem Pharmacol 68:1581-1602
Bolanos CA, Glatt SJ, Jackson D (1998) Subsensitivity to dopaminergic drugs in periadolescent rats: A behavioral and neurochemical analysis. Dev Brain Res 111:25-33
Clark DB, Thatcher DL, Tapert SF (2008) Alcohol, psychological dysregulation, and adolescent brain development. Alcohol Clin Exp Res 32:375-385
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
Doremus-Fitzwater TL, Varlinskaya EI, Spear LP (2010) Motivational systems in adolescence: Possible implications for age differences in substance abuse and other risk-taking behaviours. Brain Cogn 72:114-123
Dudek BC, Phillips TJ, Hahn ME (1991) Genetic analyses of the biphasic nature of the alcohol dose-response curve. Alcohol Clin Exp Res 15:262-269
Dudek BC, Tritto T, Underwood KA (1994) Genetic influences on locomotor activating effects of ethanol and sodium pentobarbital. Pharmacol Biochemand Behav 48:593-600
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 Behav 93:199-211
Gallegos RA, Lee RS, Criado JR, Henriksen SJ, Steffensen SC (1999) Adaptive responses of gamma-aminobutyric acid neurons in the ventral tegmental area to chronic ethanol. J Pharmacol Exp Ther 291:1045-1053
Grant KA (1999) Strategies for understanding the pharmacological effects of ethanol with drug discrimination procedures. Pharmacol Biochem Behav 64:261-267
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
Hefner K, Holmes A (2007) An investigation of the behavioral actions of ethanol across adolescence in mice. Psychopharmacology (Berl) 191:311-22
Imperato A, Di Chiera G (1986) Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219-228
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
King TS, Chinchilli VM (2001) Robust estimators of the concordance correlation coefficient. J Biopharm Stat 11:83-105
Laurie DJ, Wisden W, Seeburg PH (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J Neurosci 12:4151-4172
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
Liljequist S, Ossowska K (1994) Genotypic differences in locomotor stimulation and dopaminergic activity following acute ethanol administration. Eur Neuropsychopharmacol 4:31-38
Linsenbardt DN, Moore EM, Gross CD, Goldfarb KJ, Blackman LC, Boehm SL 2nd (2009) Sensitivity and tolerance to the hypnotic and ataxic effects of ethanol in adolescent and adult C57BL/6J and DBA/2J mice. Alcohol Clin Exp Res 33:464-476
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
Lopez M, Simpson D, White N, Randall C (2003) Age- and sexrelated differences in alcohol and nicotine effects in C57BL/6J mice. Addict Biol 8:419-427
Martz A, Deitrich RA, Harris RA (1983) Behavioral evidence for the involvement of gamma-aminobutyric acid in the actions of ethanol. Eur J Pharmacol 89:53-62
Pian JP, Criado JR, Walker BM, Ehlers CL (2008) Differential effects of acute alcohol on EEG and sedative responses in adolescent and adult Wistar rats. Brain Res 1194:28-36
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
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
SilveriMM, Spear LP (1998) Decreased sensitivity to the hypnotic effects of ethanol early in ontogeny. Alcohol Clin Exp Res 22:670-676
Silveri MM, Spear LP (2000) Ontogeny of ethanol elimination and ethanol-induced hypothermia. Alcohol 20:45-53
Silveri MM, Spear LP (2002) The effects of NMDA and GABAA pharmacological manipulations on ethanol sensitivity in immature and mature animals. Alcohol Clin Exp Res 26:449-456
Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417-463
Spear LP, Varlinskaya EI (2005) Adolescence. Alcohol sensitivity, tolerance, and intake. Recent Dev Alcohol 17:143-159
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
Stevenson RA, Besheer J, Hodge CW (2008) Comparison of ethanol locomotor sensitization in adolescent and adult DBA/2J mice. Psychopharmacology (Berl) 197:361-370
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
Tarazi FI, Baldessarini RJ (2000) Comparative postnatal development of dopamine D(1), D(2) and D(4) receptors in rat forebrain. Int J Dev Neurosci 18:29-37
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
Tirelli E, Jodogne C, Perikel JJ (1991) Adult-like biphasic neurobehavioral changes induced by a GABA-A agonist in infant and weanling mice. Brain Res Dev Brain Res 61:207-215
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
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
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
Walker QD, Morris SE, Arrant AE, Nagel JM, Parylak S, Zhou G, Caster JM, Kuhn CM (2010) Dopamine uptake inhibitors but not dopamine releasers induce greater increases in motor behavior and extracellular dopamine in adolescent than adult male rats. J Pharmacol Exp Ther (in press)
Webb B, Burnett PW, Walker DW (2002) Sex differences in ethanolinduced hypnosis and hypothermia in young Long-Evans rats. Alcohol Clin Exp Res 26:695-704
White AM, Swartzwelder HS (2005) Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults. Recent Dev Alcohol 17:161-176
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
Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469-492
Xia Y, Haddad GG (1992) Ontogeny and distribution of GABAA receptors in rat brainstem and rostral brain regions. Neuroscience 49:973-989
