Selective blockade of spinal D2DR by levo-corydalmine attenuates morphine tolerance via suppressing PI3K/Akt-MAPK signaling in a MOR-dependent manner

Abstract

Pain medicine: why blocking dopamine receptors alleviates morphine tolerance By blocking dopamine receptors located in the spinal cord, a compound found in a traditional Chinese herbal medicine may help mitigate tolerance to morphine, a common problem among cancer patients who regularly take the opioid painkiller. A team led by Ji-Hua Liu and Bo-Yang Yu from China Pharmaceutical University in Nanjing had previously showed that inhibiting dopamine D2 receptors in spinal neurons prevented mice from developing morphine tolerance, but it wasn’t clear why. They have now demonstrated that blocking D2 receptors prevents the relay of cellular signals from morphine-binding “μ-opioid” receptors to mediators of drug tolerance. Levo-corydalmine, a compound isolated from the Asian Corydalis plant, binds and inhibits D2 receptors. When administered directly into the spinal cords of mice and rats, it blocked downstream signaling, reducing morphine tolerance.