l-Stepholidine Blocks Methamphetamine-Induced Locomotor Sensitization in Mice

Repeating administration of methamphetamine (METH) can result in locomotor sensitization, a progressive increase in their psychomotor activating effects. l-Stepholidine (l-SPD), an alkaloid extract of the Chinese herb Stephania intermedia, is the first compound known to exhibit mixed dopamine D1 receptor agonist/D2 antagonist properties and is a potential medication for the treatment of drug addiction. Therefore, the effects of l-SPD on the hyperactivity, development and expression of METH-induced locomotor sensitization were investigated. The results indicated that l-SPD dose-dependently inhibited hyperlocomotion induced by acute METH and prevented the sensitized motor behavior induced by chronic METH administration. l-SPD likely acts as a D1 partial agonist and a D2 antagonist to produce its in vivo effects and may be a promising agent for treatment of METH addiction.