Long-term exposure to daily ethanol injections in DBA/2J and Swiss mice: Lessons for the interpretation of ethanol sensitization

Most mice ethanol sensitization studies focused on neurobiology at the expense of its behavioral characterization. Furthermore, relatively short ethanol exposures (10 to 20 injections) were used in these studies. The first aim of the present study is to better characterize the development and expression of ethanol sensitization after an extended exposure of 45 daily injections. In some previous studies, mice were classified as “respondent” and “resistant” to ethanol sensitization. The second aim of the present study is to test the long-term reliability of such categorizations and the consequences of their use on the interpretation of the ethanol sensitization results. Swiss and DBA2/j female mice received 45 consecutive daily ethanol administrations (respectively 2.5 and 2.0 g/kg) and their locomotor activity was daily recorded to test the development of ethanol sensitization. At the end of the procedure, a challenge test assessed the inter-group ethanol sensitization. The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA2/j mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. Remarkably, ethanol sensitization after such a long daily ethanol treatment resulted in both an upward shift of the magnitude of ethanol stimulant effects and a prolongation of these effects in time (up to 30 minutes). Mice classified as “resistant to ethanol sensitization” according to previous studies developed very significant levels of ethanol sensitization when tested after 45 ethanol injections and are best described as showing a delayed development of ethanol sensitization. Furthermore, mice classified as respondent or resistant to ethanol sensitization also differ in their acute response to ethanol, such that it is difficult to ascertain whether these classifications are specifically related to the sensitization process.

[1]  J. Nobrega,et al.  A role for nucleus accumbens glutamate in the expression but not the induction of behavioural sensitization to ethanol , 2018, Behavioural Brain Research.

[2]  M. Naassila,et al.  Resistance to ethanol sensitization is associated with a loss of synaptic plasticity in the hippocampus , 2017, Synapse.

[3]  R. Camarini,et al.  Behavioral sensitization to ethanol: Neural basis and factors that influence its acquisition and expression , 2016, Brain Research Bulletin.

[4]  E. Quertemont,et al.  Differential effects of context on psychomotor sensitization to ethanol and cocaine , 2016, Behavioural pharmacology.

[5]  J. Nobrega,et al.  Localized brain differences in Arc expression between mice showing low vs. high propensity to ethanol sensitization , 2016, Pharmacology Biochemistry and Behavior.

[6]  J. Nobrega,et al.  Changes in dendritic spine density in the nucleus accumbens do not underlie ethanol sensitization , 2015, Synapse.

[7]  K. P. Abrahao,et al.  Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses , 2014, Front. Behav. Neurosci..

[8]  K. P. Abrahao,et al.  Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens , 2014, PloS one.

[9]  J. Jeanblanc,et al.  Deciphering the relationship between vulnerability to ethanol‐induced behavioral sensitization and ethanol consumption in outbred mice , 2014, Addiction biology.

[10]  J. Nobrega,et al.  Altered NMDA receptor subunit gene expression in brains of mice showing high vs. low sensitization to ethanol , 2014, Behavioural Brain Research.

[11]  K. P. Abrahao,et al.  Expression of behavioral sensitization to ethanol is increased by energy drink administration , 2013, Pharmacology Biochemistry and Behavior.

[12]  M. Naassila,et al.  Blockade of ethanol-induced behavioral sensitization by sodium butyrate: descriptive analysis of gene regulations in the striatum. , 2013, Alcoholism, clinical and experimental research.

[13]  J. Nobrega,et al.  Susceptibility to ethanol sensitization is differentially associated with changes in pCREB, trkB and BDNF mRNA expression in the mouse brain , 2013, Behavioural Brain Research.

[14]  J. Weiner,et al.  Locomotor Sensitization to Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Nucleus Accumbens and Increases Ethanol Self-Administration , 2013, The Journal of Neuroscience.

[15]  K. P. Abrahao,et al.  Behavioral sensitization to ethanol results in cross-sensitization to MK-801 but not to NMDA administered intra-accumbens , 2012, Behavioural Brain Research.

[16]  M. Naassila,et al.  Expression of Ethanol-Induced Behavioral Sensitization Is Associated with Alteration of Chromatin Remodeling in Mice , 2012, PloS one.

[17]  E. Quertemont,et al.  Chronic ethanol exposure during adolescence alters the behavioral responsiveness to ethanol in adult mice , 2012, Behavioural Brain Research.

[18]  K. P. Abrahao,et al.  Accumbal dopamine D2 receptor function is associated with individual variability in ethanol behavioral sensitization , 2012, Neuropharmacology.

[19]  E. Quertemont,et al.  Developmental differences in ethanol-induced sensitization using postweanling, adolescent, and adult Swiss mice , 2012, Psychopharmacology.

[20]  S. Tufik,et al.  Effects of group exposure on single injection-induced behavioral sensitization to drugs of abuse in mice. , 2011, Drug and alcohol dependence.

[21]  A. Ferrara,et al.  Do excitatory and inhibitory conditioning processes underlie psychomotor sensitization to amphetamine? An analysis using simple and multiple regressions , 2011, Behavioural Brain Research.

[22]  R. Camarini,et al.  Behavioral and neurochemical studies in distinct animal models of ethanol's motivational effects. , 2010, Current drug abuse reviews.

[23]  K. P. Abrahao,et al.  Individual differences to repeated ethanol administration may predict locomotor response to other drugs, and vice versa , 2009, Behavioural Brain Research.

[24]  S. Tufik,et al.  Ethanol-induced behavioral sensitization is associated with dopamine receptor changes in the mouse olfactory tubercle , 2009, Physiology & Behavior.

[25]  C. Scavone,et al.  Environmental modulation of ethanol-induced locomotor activity: Correlation with neuronal activity in distinct brain regions of adolescent and adult Swiss mice , 2008, Brain Research.

[26]  K. P. Abrahao,et al.  Morphine attenuates the expression of sensitization to ethanol, but opioid antagonists do not , 2008, Neuroscience.

[27]  Y. Itzhak,et al.  Ethanol-induced behavioral sensitization in adolescent and adult mice: role of the nNOS gene. , 2008, Alcoholism, clinical and experimental research.

[28]  E. Quertemont,et al.  Parametric analysis of the development and expression of ethanol-induced behavioral sensitization in female Swiss mice: effects of dose, injection schedule, and test context , 2008, Psychopharmacology.

[29]  Patrick Royston,et al.  The cost of dichotomising continuous variables , 2006, BMJ : British Medical Journal.

[30]  R. Silva,et al.  Drug-induced home cage conspecifics' behavior can potentiate behavioral sensitization in mice , 2006, Pharmacology Biochemistry and Behavior.

[31]  Douglas G Altman,et al.  Dichotomizing continuous predictors in multiple regression: a bad idea , 2006, Statistics in medicine.

[32]  J. Nobrega,et al.  Increased brain dopamine D4-like binding after chronic ethanol is not associated with behavioral sensitization in mice. , 2005, Alcohol.

[33]  H. Kayir,et al.  Investigation of the effects of tianeptine and fluoxetine on pentylenetetrazole-induced seizures in rats. , 2005, Journal of psychiatric research.

[34]  E. Quertemont,et al.  Influence of the dose and the number of drug-context pairings on the magnitude and the long-lasting retention of cocaine-induced conditioned place preference in C57BL/6J mice , 2005, Psychopharmacology.

[35]  G. McClelland,et al.  Negative Consequences of Dichotomizing Continuous Predictor Variables , 2003 .

[36]  P. Meyer,et al.  Bivalent effects of MK-801 on ethanol-induced sensitization do not parallel its effects on ethanol-induced tolerance. , 2003, Behavioral neuroscience.

[37]  J. Nobrega,et al.  Is behavioral sensitization to ethanol associated with contextual conditioning in mice? , 2003, Behavioural pharmacology.

[38]  H. Sershen,et al.  Strain and sex differences in repeated ethanol treatment‐induced motor activity in quasi‐congenic mice , 2002, Genes, brain, and behavior.

[39]  J. Nobrega,et al.  Differential propensity to ethanol sensitization is not associated with altered binding to D1 receptors or dopamine transporters in mouse brain , 2002, Addiction biology.

[40]  J. Nobrega,et al.  Resistance to ethanol sensitization is associated with increased NMDA receptor binding in specific brain areas. , 2002, European journal of pharmacology.

[41]  J. Martín,et al.  Blockade of alcohol-induced locomotor sensitization and conditioned place preference in DBA mice by 7-nitroindazole , 2000, Brain Research.

[42]  J. Nobrega,et al.  Sensitization to ethanol’s stimulant effect is associated with region-specific increases in brain D2 receptor binding , 1999, Psychopharmacology.

[43]  D. Newlin,et al.  Chronic tolerance and sensitization to alcohol in sons of alcoholics: II. Replication and reanalysis. , 1999, Experimental and clinical psychopharmacology.

[44]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[45]  W. Lands,et al.  A role for behavioral sensitization in uncontrolled ethanol intake. , 1992, Alcohol.

[46]  P. Kalivas,et al.  Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity , 1991, Brain Research Reviews.

[47]  D. Newlin,et al.  Alcohol challenge with sons of alcoholics: a critical review and analysis. , 1990, Psychological bulletin.

[48]  H. June,et al.  Neurobehavioral studies of ethanol reward and activation. , 1990, Alcohol.

[49]  M. L. Souza,et al.  The excitatory effect of ethanol: Absence in rats, no tolerance and increased sensitivity in mice , 1986, Pharmacology Biochemistry and Behavior.

[50]  J. Masur,et al.  The excitatory component of ethanol in mice: A chronic study , 1980, Pharmacology Biochemistry and Behavior.

[51]  M. Naassila,et al.  Basal anxiety negatively correlates with vulnerability to ethanol-induced behavioral sensitization in DBA/2J mice: modulation by diazepam. , 2015, Alcoholism, clinical and experimental research.

[52]  L. Vanderschuren,et al.  Sensitization processes in drug addiction. , 2010, Current topics in behavioral neurosciences.

[53]  R. Lister,et al.  Time course of ethanol's effects on locomotor activity, exploration and anxiety in mice , 2006, Psychopharmacology.

[54]  M. S. Berry,et al.  Time course of the locomotor stimulant and depressant effects of a single low dose of ethanol in mice , 2004, Psychopharmacology.

[55]  Kristopher J Preacher,et al.  On the practice of dichotomization of quantitative variables. , 2002, Psychological methods.

[56]  D. Newlin,et al.  Chronic tolerance and sensitization to alcohol in sons of alcoholics: II. Replication and reanalysis , 1999 .

[57]  R. Post,et al.  CONDITIONED COMPONENTS OF COCAINE SENSITIZATION , 1992, Clinical neuropharmacology.