Specific Inhibition of Interpeduncular Nucleus GABAergic Neurons Alleviates Anxiety-Like Behaviors in Male Mice after Prolonged Abstinence from Methamphetamine.
J Neurosci
; 43(5): 803-811, 2023 02 01.
Article
em En
| MEDLINE
| ID: mdl-36564185
ABSTRACT
Anxiety is one of the most common withdrawal symptoms of methamphetamine (METH) abuse, which further drives relapse to drugs. Interpeduncular nucleus (IPN) has been implicated in anxiety-like behaviors and addiction, yet its role in METH-abstinence-induced anxiety remains unknown. Here, we found that prolonged abstinence from METH enhanced anxiety-like behaviors in male mice, accompanied by more excited IPN GABAergic neurons, as indicated by the increased c-fos expression and the enhanced neuronal excitability by electrophysiological recording in the GABAergic neurons. Using the designer receptors exclusively activated by designer drugs method, specific inhibition of IPN GABAergic neurons rescued the aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduced anxiety-like behaviors, whereas it did not induce depression-like behaviors in male mice after prolonged abstinence from METH. These findings reveal that IPN GABAergic neurons should be a promising brain target to alleviate late withdrawal symptoms from METH with few side effects.SIGNIFICANCE STATEMENT Prolonged abstinence from METH triggers IPN GABAergic neurons and ultimately increases anxiety in male mice. Suppressing IPN GABAergic neurons rescues METH abstinence-induced aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduces anxiety in mice.
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Abstinência a Substâncias
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Transtornos Relacionados ao Uso de Anfetaminas
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Núcleo Interpeduncular
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Metanfetamina
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article