Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal.
Proc Natl Acad Sci U S A
; 115(16): 4282-4287, 2018 04 17.
Article
en En
| MEDLINE
| ID: mdl-29610348
ABSTRACT
Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the AMP-activated protein kinase (AMPK) pathway in the hippocampus is activated following chronic nicotine use, an effect that is rapidly reversed by nicotine withdrawal. Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal. We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKα subunits within the hippocampus. This study provides evidence of a direct effect of AMPK modulation on nicotine withdrawal symptoms and suggests central AMPK activation as a therapeutic target for smoking cessation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastornos de Ansiedad
/
Síndrome de Abstinencia a Sustancias
/
Proteínas Quinasas Activadas por AMP
/
Hipocampo
/
Metformina
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Proteínas del Tejido Nervioso
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Nicotina
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article