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Papers of the Week

Papers: 22 May 2021 - 28 May 2021

Animal Studies, Pharmacology/Drug Development

2021 May 24

Mol Pharmacol

ABIN-1 in the brain alleviated opioid tolerance through its action on β-arrestin2.


Zhang Y, Zhou P, Lu F, Su R, Gong Z
Mol Pharmacol. 2021 May 24.
PMID: 34031190.


Opioids play an important role in pain relief, but repeated exposure results in tolerance and dependence. To make opioids more effective and useful, research in the field has focused on reducing the tolerance and dependence for chronic pain relief. Here, we showed the effect of ABIN-1 in modulating morphine function. We used hotplate tests and CPP tests to show that overexpression of ABIN-1 in the mice brain attenuated morphine dependence. These effects of ABIN-1 are most likely mediated through the formation of ABIN-1-β-arrestin2 complexes, which accelerate β-arrestin2 degradation by ubiquitination. With the degradation of β-arrestin2, ABIN-1 overexpression also decreased MOR phosphorylation and internalization following opioid treatment, affecting the β-arrestin2-dependent signaling pathway to regulate morphine tolerance. Importantly, the effect of ABIN-1 on morphine tolerance was abolished in β-arrestin2 knockout mice. Taken together, these results suggest that the interaction between ABIN-1 and β-arrestin2 inhibits MOR internalization to attenuate morphine tolerance, revealing a novel mechanism for MOR regulation. Hence, ABIN-1 may be a therapeutic target to regulate MOR internalization, thus providing a foundation for a novel treatment strategy for alleviating morphine tolerance and dependence. ABIN-1 overexpression in mice brain attenuated morphine tolerance and dependence. The mechanism may be that ABIN-1-β-arrestin-2 complex formation facilitated β-arrestin-2 degradation by ubiquitination. ABIN-1 targeted β-arrestin2 to regulate morphine tolerance Therefore, inhibiting of ABIN-1 is an important strategy to prevent morphine tolerance and dependence.