» The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence. Fabrice Trovero, Sabrina David, Philippe Bernard, Alain Puech, Jean-Charles Bizot, Jean-Pol Tassin. 2016 PLOSone
» Sensitization to the Stimulant Motor Effects of Ethanol Is Not Dependent On Tolerance to Ataxic or Sedative Properties of Ethanol in Female Mice. R Legastelois, B Botia and M Naassila. Accepté dans
J Alcohol Drug Depend 2015Ethanol (EtOH)-induced behavioral sensitization (EIBS) is defined as an enhancement of locomotor activity following repeated EtOH exposure and is proposed to reflect an increase in EtOH “wanting”. However, the reliability of the sensitization model in studying addiction is still a matter of debate. One major criticism is that the increase in locomotion occurring during sensitization may be a by-product of tolerance to the ataxic and/or sedative effects of EtOH. We investigated the relationship between EIBS amplitude and sensitivity to EtOH-induced ataxia and sedation after the development of tolerance to EtOH depressant effects in adult female DBA/2J mice. After receiving daily injection of saline or 2 g/kg EtOH during 10 consecutive days to induce EIBS, recovery from acute motor incoordination produced by ethanol (2 g/kg EtOH using rotarod) and from loss of righting reflex (4 g/kg EtOH) was measured. We showed that induction of EtOH sensitization after repeated administration of EtOH is associated with a more rapid recovery from acute motor incoordination and from sedation produced by ethanol when compared to the acute groups, suggesting the development of tolerance to the ataxic and sedative effects of EtOH. However, correlational analyses failed to detect any relationship between EIBS amplitude and the response to EtOH ataxic or sedative effects. Altogether, our results confirm and extend previous data showing a tolerance to the ataxic and sedative properties of EtOH after repeated exposure to EtOH and suggest that this tolerance is not related to the amplitude of EIBS.
Basal Anxiety Negatively Correlates With Vulnerability to Ethanol-Induced Behavioral Sensitization in DBA/2J Mice: Modulation by Diazepam. October 2014
Béatrice Botia*, Rémi Legastelois*, Hakim Houchi, and Mickael Naassilatélécharger la publicationBackground:Anxiety disorders predispose individuals to the development of alcohol dependence in humans. Surprisingly, whether anxiety is a trait influencing the development of alcohol-related behav- iors in rodents remains controversial. Here, we addressed the hypothesis of a relationship between basal anxiety levels and the development of ethanol (EtOH)-induced behavioral sensitization (EIBS), a model of neuroadaptations occurring after repeated EtOH exposure which is proposed to play a role in early and recurring steps of addiction.
Methods:EtOH-na€ıve DBA/2J mice were submitted to the elevated plus maze and light/dark box tests to evaluate their basal anxiety levels. Then, mice received daily i.p. injection of saline or 2 g/kg EtOH for 10 days and locomotor activity was immediately monitored. Mice were then split into resis- tant and sensitized phenotypes based on their increase in locomotion. The relationship between basal anxiety and the development of sensitization was investigated. In addition, we tested the effect of an 8-day-long treatment with 4 mg/kg diazepam, a broad-spectrum benzodiazepine anxiolytic, on the expression of sensitization in both resistant and sensitized mice.
Results:For the first time, we showed that vulnerability to EIBS is negatively correlated with basal anxiety. Moreover, a diazepam treatment during EIBS procedure increased EtOH-induced hyperloco- motion of resistant mice after 1 week of withdrawal (but not immediately after) without any effect in the group of sensitized mice.
Conclusion:This study shows that, in mice, basal anxiety predicts the vulnerability to EIBS. Mice exhibiting low basal anxiety will develop higher EIBS than mice with elevated anxiety levels. Modula- tion of anxiety by a diazepam treatment during the development of EIBS enhances its expression after 1 week postinduction. Altogether, we demonstrated an inverse relationship between basal anxiety-like behaviors and EIBS vulnerability and that resistance to EIBS vanishes after anxiolytic treatment.
Key Words:Anxiety, Behavioral Sensitization, Diazepam, Ethanol, Interindividual Variability.
Deciphering the relationship between vulnerability to ethanol-induced behavioral sensitization and ethanol consumption in outbred mice. September 2013
Rémi Legastelois, Béatrice Botia, Fabien Coune, Jérôme Jeanblanc and Mickaël Naassila
Addiction BiologyEdited By: Rainer Spanagel, Editor for North America: Markus Heilig
Impact Factor: 5.914
ISI Journal Citation Reports © Ranking: 2012: 1/16 (Substance Abuse); 42/290 (Biochemistry & Molecular Biology)
Online ISSN: 1369-1600
Associated Title(s):
Addictiontélécharger la publicationBlockade of Ethanol-Induced Behavioral Sensitization by Sodium Butyrate: Descriptive Analysis of Gene Regulations in the Striatum.
Legastelois R, Botia B, Naassila M.
Alcohol Clin Exp Res. 2013 Mar 12. doi: 10.1111/acer.12088. télécharger la publicationAbstract
BACKGROUND: Behavioral sensitization induced by repeated ethanol (EtOH) exposure may play a critical role in the development of alcohol dependence. Because recent data demonstrate that histone deacetylase inhibitor (HDACi) may be of interest in the treatment of addiction, we explored the effect of the HDACi sodium butyrate (NaB) on EtOH-induced behavioral sensitization (EIBS) in DBA/2J mice. We also investigated gene regulations in the striatum of sensitized mice using epigenetic- and signal transduction-related PCR arrays.
METHODS: Mice were injected with saline or EtOH (0.5 to 2.5 g/kg) once a day for 10 days. Mice received NaB (200 to 600 mg/kg) 30 minutes before each injection (prevention protocol) or once daily between days 11 and 16 (reversal protocol). At day 17, brains were removed 30 minutes after a saline or EtOH challenge to assess gene and proteins levels.
RESULTS: Only the intermediate EtOH doses (1.0 and 2.0 g/kg) were effective in inducing EIBS, and both doses were associated with specific gene regulations in the striatum. The induction of sensitization by 1.0 g/kg (but not 2.0 g/kg) EtOH was dose-dependently prevented or reversed by NaB. Among the 168 studied genes, EIBS blockade was associated with specific gene regulations (bcl-2, bdnf, hdac4, pak1, penk, tacr1, vip…) and changes in brain-derived neurotrophic factor in both striatum and prefrontal cortex.
CONCLUSIONS: These results indicate that EIBS is associated with specific gene regulations in the striatum depending on the EtOH dose and that NaB can be useful in blocking some long-lasting neuro-adaptations to repeated EtOH administrations.
Copyright © 2013 by the Research Society on Alcoholism.
PMID: 23488934
Expression of ethanol-induced behavioral sensitization is associated with alteration of chromatin remodeling in mice.
Botia B, Legastelois R, Alaux-Cantin S, Naassila M.PLoS One. 2012;7(10):e47527. doi: 10.1371/journal.pone.0047527. Epub 2012 Oct 22.
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