English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Inhibition of the Casein-Kinase-1-Epsilon/Delta Prevents Relapse-Like Alcohol Drinking

Perreau-Lenz, S., Vengeliene, V., Noori, H., Merlo-Pich, E., Corsi, M., Corti, C., et al. (2012). Inhibition of the Casein-Kinase-1-Epsilon/Delta Prevents Relapse-Like Alcohol Drinking. Neuropsychopharmacology, 37(9), 2121-2131. doi:10.1038/npp.2012.62.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0001-852B-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-852C-8
Genre: Journal Article

Files

show Files

Locators

show
hide
Locator:
https://www.nature.com/articles/npp201262.pdf (Publisher version)
Description:
-

Creators

show
hide
 Creators:
Perreau-Lenz, S, Author
Vengeliene, V, Author
Noori, HR1, Author              
Merlo-Pich, EV, Author
Corsi, MA, Author
Corti, C, Author
Spanagel, R, Author
Affiliations:
1Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: During the past decade, it has been shown that circadian clock genes have more than a simple circadian time-keeping role. Clock genes also modulate motivational processes and have been implicated in the development of psychiatric disorders such as drug addiction. Recent studies indicate that casein-kinase 1ɛ/δ (CK1ɛ/δ)—one of the components of the circadian molecular clockwork—might be involved in the etiology of addictive behavior. The present study was initiated to study the specific role of CK1ɛ/δ in alcohol relapse-like drinking using the ‘Alcohol Deprivation Effect’ model. The effect of CK1ɛ/δ inhibition was tested on alcohol consumption in long-term alcohol-drinking rats upon re-exposure to alcohol after deprivation using a four-bottle free-choice paradigm with water, 5%, 10%, and 20% ethanol solutions, as well as on saccharin preference in alcohol-naive rats. The inhibition of CK1ɛ/δ with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats. The impact of the treatment was further characterized using nonlinear regression analyses on the daily profiles of drinking and locomotor activity. We reveal that CK1ɛ/δ inhibition blunted the high daytime alcohol intake typically observed upon alcohol re-exposure, and induced a phase shift of locomotor activity toward daytime. Only the highest dose of PF-670462 shifted the saccharin intake daily rhythm toward daytime during treatment, and decreased saccharin preference after treatment. Our data suggest that CK1 inhibitors may be candidates for drug treatment development for alcoholism.

Details

show
hide
Language(s):
 Dates: 2012-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/npp.2012.62
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Neuropsychopharmacology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 37 (9) Sequence Number: - Start / End Page: 2121 - 2131 Identifier: -