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The delta opioid receptor agonist KNT-127 relieves innate anxiety-like behavior in mice by suppressing transmission from the prelimbic cortex to basolateral amygdala.
Kawaminami, Ayako; Yamada, Daisuke; Yoshioka, Toshinori; Hatakeyama, Azumi; Nishida, Moeno; Kajino, Keita; Saitoh, Tsuyoshi; Nagase, Hiroshi; Saitoh, Akiyoshi.
Afiliação
  • Kawaminami A; Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
  • Yamada D; Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
  • Yoshioka T; Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
  • Hatakeyama A; Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
  • Nishida M; Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
  • Kajino K; International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba, Japan.
  • Saitoh T; International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba, Japan.
  • Nagase H; University of Tsukuba, Tsukuba, Japan.
  • Saitoh A; Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
Neuropsychopharmacol Rep ; 44(1): 256-261, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38156409
ABSTRACT

AIM:

Excitatory projections from the prelimbic cortex (PL) to the basolateral nucleus of the amygdala (BLA) are implicated in the regulation of anxiety-like behaviors, and we previously demonstrated that anxiolytic-like effects of the selective delta-opioid receptor (DOP) agonist KNT-127 is involved in suppressing glutamate neurotransmission in the PL. Here, we investigated the mechanisms underlying the anxiolytic-like effect of KNT-127 in mice by combining optogenetic stimulation of the PL-BLA pathway with behavioral analyses.

METHODS:

Four-week-old male C57BL/6J mice received bilateral administration of adeno-associated virus (AAV)2-CaMKIIa-hChR2(H134R)-enhanced yellow fluorescent protein (EYFP) into the PL to induce expression of the light-activated excitatory ionic channel ChR2. Subsequently, an optic fiber cannula connected to a wireless photo-stimulator was implanted into the BLA for optogenetic PL-BLA pathway stimulation. We evaluated innate anxiety using the elevated plus maze (EPM) and open field (OF) tests as well as learned anxiety using the contextual fear conditioning (CFC) test.

RESULTS:

Optogenetic activation of the PL-BLA pathway enhanced anxiety-like behaviors in the EPM and OF, while prior subcutaneous administration of KNT-127 (10 mg/kg) reduced this anxiogenic effect. In contrast, optogenetic activation of the PL-BLA pathway had no significant effect on conditioned fear.

CONCLUSION:

Our findings indicate that the PL-BLA circuit contributes to innate anxiety and that the anxiolytic-like effects of KNT-127 are mediated at least in part by suppression of PL-BLA transmission. The PL delta-opioid receptor may thus be an effective therapeutic target for anxiety disorders.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ansiolíticos / Complexo Nuclear Basolateral da Amígdala / Morfinanos Limite: Animals Idioma: En Revista: Neuropsychopharmacol Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ansiolíticos / Complexo Nuclear Basolateral da Amígdala / Morfinanos Limite: Animals Idioma: En Revista: Neuropsychopharmacol Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos