Distinct Amygdala Neuronal Populations Control Opioid Use and Withdrawal in Mice.

BACKGROUND Opioid use disorder (OUD) is a chronic and recurring psychiatric disorder that is associated with high morbidity and mortality. The central nucleus of the amygdala (CeA) undergoes neuroadaptations in both humans with OUD and opioid-dependent rodents. As part of a heterogeneous microcircuits, the CeA integrates internal and external sensory inputs that drive innate and adaptive behaviors. Key CeA neuronal populations, including protein kinase C-δ (PKC-δ), corticotropin-releasing factor (CRF), and somatostatin (SST) neurons, regulate behaviors that are disrupted in addiction, such as pain, stress, reward function, and anxiety/arousal. We hypothesized that these CeA neuronal populations differentially regulate opioid-related behaviors. METHODS We used in situ hybridization to characterize the expression of μ-opioid receptor (MOR; Oprm1), and to assess the functional role of these CeA neuronal populations, we used behavioral and molecular approaches in opioid-dependent mice. RESULTS We identified a decrease Oprm1 mRNA expression in the CeA in opioid-dependent mice that were undergoing withdrawal compared with nondependent mice. In contrast, the expression of PKC-δ (Prkcd), CRF (Crh), and SST (Sst) mRNA levels remained unchanged. The chemogenetic inhibition of CeAPKC-δ neurons decreased fentanyl vapor self-administration and alleviated fentanyl withdrawal-induced hyperalgesia. The inhibition of CeACRF neurons reduced irritability and somatic withdrawal signs. The activation of CeASST neurons reduced somatic withdrawal signs. CONCLUSIONS These findings suggest that distinct CeA neuronal populations uniquely regulate different aspects of opioid use and withdrawal, highlighting cell-type specific targets for potential therapeutic interventions.

• Publication year

  2025

• Venue

  Biological Psychiatry

• Publication date

  2025-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.biopsych.2025.08.021PMID 40935226
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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