Agonist-Promoted Phosphorylation and Internalization of the Kappa Opioid Receptor in Mouse Brains: Lack of Connection With Conditioned Place Aversion.
Frontiers in Pharmacology January 1, 2022 Chongguang Chen, Peng Huang, Kathryn Bland et al.
Selective kappa opioid receptor (KOR) agonists are promising for treating pain and itch but often cause side effects like dysphoria and sedation. This study tested whether conditioned place aversion (CPA), a measure of dysphoria, is linked to KOR phosphorylation and internalization—markers of β-arrestin recruitment—in male mice. Using four KOR agonists at doses that maximally reduce pain and scratching, the authors found that U50,488H, MOM-SalB, and 42B, but not nalfurafine, induced KOR phosphorylation and internalization in brain regions. Yet, prior work showed that U50,488H and MOM-SalB cause CPA, while nalfurafine and 42B do not. These results indicate no connection between CPA and these β-arrestin-related processes.