L-Tetrahydropalmatine inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal activity and dopamine D3 receptor expression

Methamphetamine (METH) is a psychomotor stimulant that produces hyperlocomotion in rodents. L-tetrahydropalmatine (L-THP) is an active ingredient found in Corydalis ternata which has been used as a traditional herbal preparation in Asian countries for centuries, however, the effect of L-THP on METH-induced phenotypes largely unknown. In this study, to evaluate the effect of L-THP on METH-induced psychotropic effects, rats were pretreated with L-THP (10 and 15 mg/kg) before acute METH injection, following which the total distance the rats moved in an hour was measured. To clarify a possible mechanism underlying the effect of L-THP on METH-induced behavioral changes, dopamine receptor mRNA expression levels in the striatum of the rats was measured following the locomotor activity study. In addition, the effect of L-THP (10 and 15 mg/kg) on serotonergic (5-HTergic) neuronal pathway activation was studied by measurement of 5-HT (80 mu g/10 mu l/mouse)-induced head twitch response (HTR) in mice. L-THP administration significantly inhibited both hyperlocomotion in rats and HTR in mice. L-THP inhibited climbing behavior-induced by dopaminergic (DAergic) neuronal activation in mice. Furthermore, L-THP attenuated the decrease in dopamine D3 receptor mRNA expression levels in the striatum of the rats induced by METH. These results suggest that L-THP can ameliorate behavioral phenotype induced by METH through regulation of 5-HT neuronal activity and dopamine D3 receptor expression. (C) 2014 Elsevier GmbH. All rights reserved.