RT Journal Article
SR Electronic
T1 Angiotensin-converting enzyme governs endogenous opioid signaling and synaptic plasticity in nucleus accumbens
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.08.459469
DO 10.1101/2021.09.08.459469
A1 Trieu, Brian H.
A1 Remmers, Bailey C.
A1 Toddes, Carlee
A1 Brandner, Dieter D.
A1 Xie, Wei
A1 More, Swati S.
A1 Rothwell, Patrick E.
YR 2021
UL http://biorxiv.org/content/early/2021/09/09/2021.09.08.459469.abstract
AB Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is expressed at uniquely high levels in the striatonigral pathway, but its central function remains poorly understood. We find that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced mu 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 decreased the conditioned place preference caused by fentanyl administration, and enhanced reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit, while mitigating risk of addiction.Competing Interest StatementThe authors have declared no competing interest.