Titre du document / Document title

The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption

Auteur(s) / Author(s)

SPANAGEL Rainer ; PENDYALA Gurudutt ; ABARCA Carolina ; ZGHOUL Tarek ; SANCHIS-SEGURA Caries ; MAGNONE Maria Chiara ; LASCORZ Jesus ; DEPNER Martin ; HOLZBERG David ; SOYKA Michael ; SCHREIBER Stefan ; MATSUDA Fumihiko ; LATHROP Mark ; SCHUMANN Gunter ; ALBRECHT Urs ;

Résumé / Abstract

Period (Per) genes are involved in regulation of the circadian clock and are thought to modulate several brain functions. We demonstrate that Per2_Brdm1 mutant mice, which have a deletion in the PAS domain of the Per2protein, show alterations in the glutamatergic system. Lowered expression of the glutamate transporter Eaat1 is observed in these animals, leading to reduced uptake of glutamate by astrocytes. As a consequence, glutamate levels increase in the extracellular space of Per2_Brdm1 mutant mouse brains. This is accompanied by increased alcohol intake in these animals. In humans, variations of the PER2 gene are associated with regulation of alcohol consumption. Acamprosate, a drug used to prevent craving and relapse in alcoholic patients is thought to act by dampening a hyper-glutamatergic state. This drug reduced augmented glutamate levels and normalized increased alcohol consumption in Per2_Brdm1 mutant mice. Collectively, these data establish glutamate as a link between dysfunction of the circadian clock gene Per2 and enhanced alcohol intake.

Revue / Journal Title

Nature medicine   ISSN 1078-8956 

Source / Source

2005, vol. 11, n^o1, pp. 35-42 [8 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing Group, New York, NY, ETATS-UNIS  (1995) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 26326, 35400012700150.0030