Ethanol-Sensitive Brain Regions in Rat and Mouse: A Cartographic Review, Using Immediate Early Gene Expression

Authors

  • Catherine Vilpoux,

    1. From the Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, and Institut Fédératif de Recherche 114, Institut de Médecine Prédictive et de Recherche Thérapeutique (IFR 114 IMPRT), Centre Hospitalier Regional Universitaire, Lille, France.
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  • Vincent Warnault,

    1. From the Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, and Institut Fédératif de Recherche 114, Institut de Médecine Prédictive et de Recherche Thérapeutique (IFR 114 IMPRT), Centre Hospitalier Regional Universitaire, Lille, France.
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  • Olivier Pierrefiche,

    1. From the Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, and Institut Fédératif de Recherche 114, Institut de Médecine Prédictive et de Recherche Thérapeutique (IFR 114 IMPRT), Centre Hospitalier Regional Universitaire, Lille, France.
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  • Martine Daoust,

    1. From the Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, and Institut Fédératif de Recherche 114, Institut de Médecine Prédictive et de Recherche Thérapeutique (IFR 114 IMPRT), Centre Hospitalier Regional Universitaire, Lille, France.
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  • Mickael Naassila

    1. From the Equipe Région INSERM 24 (ERI24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, and Institut Fédératif de Recherche 114, Institut de Médecine Prédictive et de Recherche Thérapeutique (IFR 114 IMPRT), Centre Hospitalier Regional Universitaire, Lille, France.
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Reprint requests: Dr. Catherine Vilpoux, PhD, Equipe Région INSERM 24 (ERI 24), Groupe de Recherche sur l’Alcool et les Pharmacodépendances (GRAP), Université de Picardie Jules Verne, Faculté de Pharmacie, 1 rue des Louvels, Amiens 80000, France; Fax: 33 3 22 82 76 72; E-mail: catherine.vilpoux@u-picardie.fr

Abstract

Background:  Ethanol addiction has been conceptualized as a progression from occasional, impulsive use to compulsive behavior. Ethanol-dependence is a chronic pathology with repeated cycles of withdrawal, craving, and relapse. Specific molecular and cellular mechanisms underlie these transition stages.

Methods:  This review aimed at elucidating whether there are also adaptations in the pattern of brain regions responding to ethanol. This paper reviews the evidence in rodents for activation of specific brain regions, assessed by induction of IEG expression, following acute and chronic ethanol exposure.

Results:  The review sheds light on the specific patterns of response in regions of the brain to different types of ethanol exposure and shows that activation of specific brain regions may occur in particular phases of the development of ethanol addiction. Some brain regions respond consistently following acute or chronic treatments or withdrawal: the prefrontal cortex; nucleus accumbens; lateral septum; hippocampus; perioculomotor urocortin-containing cells population (pIIIu), also known as Edinger-Westphal nucleus; central nucleus of the amygdale; and the paraventricular nucleus of hypothalamus. The two last brain areas are particularly activated by relapse-inducing stressors. It is of interest that the amygdala, hippocampus, and prefrontal cortex, which belong to the reward system, are activated by cue-induced relapse to ethanol self-administration in rodents and humans, while activation of these regions is reversed with anticraving compounds. Following chronic exposure, IEG induction desensitizes while withdrawal reactivates these regions.

Discussion:  Some responding regions are implicated in reward related processes (VTA, extended amygdala, hypothalamus, hippocampus, prelimbic cortex, ventral part of lateral septum) and some others in aversive-related processes (area postrema, nucleus of solitary tract).

Conclusion:  A better understanding of the neural circuits affected by ethanol and their adaptations during the development of ethanol addiction will provide new opportunities for developing appropriate therapies.

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