Anxiolytic-like action of orally administered dl-tetrahydropalmatine in elevated plus-maze

dl-Tetrahydropalmatine (dl-THP), a naturally occurring alkaloid, has been intensively studied for its sedative and hypnotic effects. Putative explanation for its mechanism and target of action involves the dopaminergic neurotransmission system. In view of the close interactions between the dopaminergic and the GABAergic neurons in the amygdala, pharmacological effects of dl-THP were tested for activity at the GABA_A receptor benzodiazepine site (BDS). Effects of dl-THP were examined in mice employing the elevated plus-maze, the holeboard and the horizontal-wire tests. In the elevated plus-maze, mice treated with low doses of dl-THP (0.5-10 mg/kg) exhibited significant increase in the percentage of entries and time spent in open arms without altering the number of closed-arm entries when compared to the control group, indicative of its selective anxiolytic effect. In the holeboard and horizontal wire tests, where exploratory behavior and potential muscle relaxant effect were assessed, respectively, only mice treated with as much as 50 mg/kg dl-THP manifested sedation and myorelaxation, as observed in the significant decrease in the number of head dips and the decrease in the percentage of mice grasping wire in comparison to control. Notably, coadministration of the BDS antagonist flumazenil abolished the dl-THP-induced anxiolysis as seen in the reversal of the increase of both the number of entries and time spent in open arms back to basal levels in the elevated plus-maze test. The results suggest that dl-THP at defined low dosages acts as anxiolytics in mice, and the BDS mediates, at least in part, such anxiolytic effect of dl-THP.