Levo-tetrahydropalmatine attenuates nicotine-induced conditioned place preference in mice

Levo-tetrahydropalmatine (l-THP) is one of the active ingredients of the Chinese medicinal herb Corydalis ambigua. It was recently found that l-THP served as a potent antagonist for heterologously expressed human nAChRs in a SH-EP1 cell line, suggesting its potential as a new aid in smoking cessation. In the present study, the effects of l-THP on the rewarding effects of nicotine (NIC) were further evaluated using the conditioned place preference (CPP) assay. Following conditioning, mice demonstrated a CPP induced by NIC (0.5 mg/kg, free-base, i.p.), which was attenuated by l-THP (1−10 mg/kg, i.p.) in a dose-dependent manner. In addition, l-THP did not only inhibit the NIC-induced CPP initiation but also its expression. Comparisons of the effects on NIC-induced CPP among l-, dl-, and d-THP showed that l-THP and dl-THP exhibited similar inhibition, but d-THP did not. Finally, compared to regular sized l-THP (5−10 μm), the nanometer size (100−200 nm) of l-THP was also shown to have similar effects. These findings suggest that l-THP can suppress the conditioned rewarding effects of NIC and indicate that l-THP could be used as a novel therapeutic drug for NIC abuse.