heroin and stepholidine

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.

Topics: Animals; Behavior, Animal; Berberine; Conditioning, Operant; Cues; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Extinction, Psychological; Heroin; Male; Motor Activity; Narcotics; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Reinforcement, Psychology; Self Administration

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 opiate addiction. The aim of the present study was to investigate the effects of pretreatment with L-SPD on heroin-seeking behavior induced by heroin priming. Male Sprague-Dawley rats were trained to self-administer heroin (0.05mg/kg per infusion) under a fixed ratio 1 schedule for 12 consecutive days and nose-poke responding was extinguished for 12 days, after which reinstatement of drug seeking was induced by heroin priming. Pretreatment with L-SPD (2.5, 5.0 and 10.0mg/kg, i.p.) inhibited the heroin-induced reinstatement of heroin-seeking behavior. Importantly, L-SPD did not affect locomotion, indicating that the observed effects of L-SPD on reinstatement are not the result of motor impairments. The present data suggested that l-SPD inhibits heroin-induced reinstatement and its potential for the treatment of heroin relapse.

Topics: Animals; Berberine; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Extinction, Psychological; Heroin; Male; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Reinforcement, Psychology; Self Administration