Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT(1A) Receptor

Tetrahydroprotoberberines (THPBs) are isoquinoline alkaloids isolated from the Chinese herb Corydalis yanhusuo. In the present study, we performed competitive binding assays to examine the binding of l-THBr to neurotransmitter receptors known to be involved in sedation, hypnosis and anxiety. Our results show that l-THBr does not interact with GABAergic receptors but has binding affinities for dopamine and serotonin receptors. In addition, cAMP and [(35)S]GTPγS assays were used to determine the agonist or antagonist properties of l-THBr at dopamine (D(1), D(2)) or serotonin (5-HT) receptors. Our results show that l-THBr displays D(1) and D(2) antagonist and 5-HT(1A) agonist properties. Moreover, l-THBr-treated rodents exhibit anxiolytic-like effects in the light/dark box and elevated plus-maze tests, and the anxiolytic effect of l-THBr can be reduced by WAY-100635, a selective 5-HT(1A) receptor antagonist. Our results suggest that l-THBr may produce potent anxiolytic-like effects mainly through serotonin receptors.