L-Stepholidine, a naturally occurring dopamine D1 receptor agonist and D2 receptor antagonist, attenuates heroin self-administration and cue-induced reinstatement in rats.

Opiate addiction is a chronic, relapsing brain disease characterized by persistent and uncontrolled drug-seeking behavior despite negative effects. L-Stepholidine (L-SPD) is an alkaloid extract of the Chinese herb Stephania intermedia with dopamine D1 receptor partial agonistic and D2 receptor antagonistic dual actions. The unique pharmacological profile of L-SPD suggests that L-SPD may be effective for the treatment of opiate addiction. The aim of this study was to characterize the effects of L-SPD on heroin self-administration on a fixed-ratio 1 schedule and cue-induced reinstatement under an extinction/reinstatement protocol. The effect of L-SPD on the locomotor activity of heroin-free rats was also tested. We found that 2.5, 5, and 10 mg/kg of L-SPD attenuated heroin self-administration and cue-induced reinstatement without affecting locomotor activity. These results showed that L-SPD, which has dual actions on dopamine D1 and D2 receptors, attenuates heroin self-administration and cue-induced reinstatement.