Pre-extinction activation of hippocampal AMPK prevents fear renewal in mice.
Pharmacol Res
; 161: 105099, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32739427
ABSTRACT
As a type of fear relapse, fear renewal compromises the efficacy of fear extinction, which serves as the laboratory analog of exposure therapy (a therapeutic strategy for anxiety disorders). Interventions aiming to prevent fear renewal would thus benefit exposure therapy. To date, it remains unknown whether central adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation could produce inhibitory effects on fear renewal. Here, using pharmacological approach and virus-mediated gene overexpression technique, we demonstrated that activation of AMPK in dorsal hippocampus shortly before fear extinction training completely abolished subsequent fear renewal in male mice without affecting other types of fear relapse, including spontaneous recovery of fear and fear reinstatement. Furthermore, we also found that metformin, a first-line antidiabetic drug, was capable of preventing fear renewal in male mice by stimulating AMPK in dorsal hippocampus. Collectively, our study provides insight into the role of hippocampal AMPK in regulation of fear renewal and indicates that increasing activity of hippocampal AMPK can prevent fear renewal, thus enhancing the potency of exposure therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
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Ativadores de Enzimas
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Extinção Psicológica
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Proteínas Quinases Ativadas por AMP
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Medo
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Hipocampo
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Terapia Implosiva
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Metformina
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article