AI Article Synopsis
- Withdrawal from chronic opioid use leads to low dopamine levels and negative feelings, which can trigger relapse.
- Activation of μ-opioid receptors (MORs) in certain brain neurons initially suppresses inhibitory signals, but withdrawal actually enhances these signals.
- Alterations in GABA transmission due to chronic fentanyl use may create a dysfunctional brain state, contributing to anxiety and withdrawal symptoms, which could lead to relapse.
Article Abstract
Withdrawal from chronic opioid use often causes hypodopaminergic states and negative affect, which may drive relapse. Direct-pathway medium spiny neurons (dMSNs) in the striatal patch compartment contain μ-opioid receptors (MORs). It remains unclear how chronic opioid exposure and withdrawal impact these MOR-expressing dMSNs and their outputs. Here, we report that MOR activation acutely suppressed GABAergic striatopallidal transmission in habenula-projecting globus pallidus neurons. Notably, withdrawal from repeated morphine or fentanyl administration potentiated this GABAergic transmission. Furthermore, intravenous fentanyl self-administration enhanced GABAergic striatonigral transmission and reduced midbrain dopaminergic activity. Fentanyl-activated striatal neurons mediated contextual memory retrieval required for conditioned place preference tests. Importantly, chemogenetic inhibition of striatal MOR neurons rescued fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These data suggest that chronic opioid use triggers GABAergic striatopallidal and striatonigral plasticity to induce a hypodopaminergic state, which may promote negative emotions and relapse.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404641 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2023.112089 | DOI Listing |
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