Blockade of Ethanol-Induced Behavioral Sensitization by Sodium Butyrate: Descriptive Analysis of Gene Regulations in the Striatum

Abstract

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.

Addiction et régulations épigénétiques

“…Chez les rongeurs, cette approche suggère que le développement des comportements liés à l'addiction était sans doute relié à des modifications épigénétiques, même si les résultats ne sont pas toujours concordants. C'est ainsi que des inhibiteurs non sélectifs des HDAC : (1) réduisent la consommation de cocaïne pendant la phase d'acquisition de l'autoadministration, ainsi que la motivation des rats à s'autoadministrer la drogue [42] ; (2) réduisent la consommation d'éthanol par des souris et la motivation des rats à s'administrer de l'éthanol [43] ; (3) facilitent l'extinction de la préférence de place induite par la cocaïne [44] ; (4) réduisent la préférence de place induite par la nicotine, mais pas l'aversion de place provoquée par des doses plus élevées [45] ; (5) inhibent la sensibilisation comportementale provoquée par l'éthanol [46] ; et (6) réduisent le comportement de recherche de cocaïne après une période de sevrage de trois semaines (rechute) [47]. D'autre part, un traitement similaire avec souvent les mêmes Les HDAC sistent pendant une bonne partie de la vie, sous-tendraient la trace d'évènements traumatisants se produisant durant les tout premiers jours de vie.…”

Sensitization to the Stimulant Motor Effects of Ethanol Is Not Dependent On Tolerance to Ataxic or Sedative Properties of Ethanol in Female Mice

“…Acute (L) group. injection of 2 g/kg EtOH for 10 days) did not result in metabolic tolerance in DBA/2J mice [35,40,53]. It is therefore unlikely that metabolic tolerance occurred in the present experiment.…”

“…Mice were housed in groups of 10 in clear plastic cages (24 × 42 ×15 cm) and kept in a temperature (21 ± 0.5°C) and humidity-controlled (55 ± 10%) environment under an established photoperiod (07.00 -19.00 hours) with free access to food (Mouse and Rats, Maintenance, Extrudate; Provimi Kliba, Kaiseraugst, Switzerland) and tap water. In the present study, we used female mice in continuity with our previous work [13,[35][36][37][38][39][40][41] and also to keep consistency with the most relevant reports supporting our working hypothesis [37,39]. The number of animals was kept to a minimum, and all efforts were made to limit stress and to avoid animal suffering.…”

“…As an example, HAP mice developed locomotor sensitization after repeated EtOH treatment without any development of tolerance to the ataxic effect of EtOH measured by the static dowel test [16]. Moreover, EIBS can be induced by EtOH doses as low as 0.5 g/kg and 1 g/kg which do not produce sedation in C57BL/6 and DBA/2J mice, respectively [34,35]. Furthermore, we previously showed in DBA/2J mice that the sensitized stimulant locomotor effect of EtOH occurs predominantly during the first 15 min following an EtOH challenge and that no locomotor tolerance is detected after 15 min, when EtOH depressant effect arises [35].…”

“…Moreover, EIBS can be induced by EtOH doses as low as 0.5 g/kg and 1 g/kg which do not produce sedation in C57BL/6 and DBA/2J mice, respectively [34,35]. Furthermore, we previously showed in DBA/2J mice that the sensitized stimulant locomotor effect of EtOH occurs predominantly during the first 15 min following an EtOH challenge and that no locomotor tolerance is detected after 15 min, when EtOH depressant effect arises [35]. In addition, the NMDA antagonist MK-801 alters EIBS in DBA/2J mice but has no effect on the development of tolerance to ataxia [36].…”