Angiotensin-converting enzyme gates brain circuit-specific plasticity via an endogenous opioid.
Science
; 375(6585): 1177-1182, 2022 03 11.
Article
em En
| MEDLINE
| ID: mdl-35201898
ABSTRACT
Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is especially abundant in striatal tissue, but the function of ACE in striatal circuits remains poorly understood. We found that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced µ-opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type-specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but it led to a decrease in conditioned place preference caused by fentanyl administration and an enhancement of reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit while mitigating the risk of addiction.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encefalina Metionina
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Peptidil Dipeptidase A
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Plasticidade Neuronal
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Núcleo Accumbens
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article