| In vivo: |
| Neuroreport. 2014 Jan 8;25(1):7-11. | | L-Stepholidine, a naturally occurring dopamine D1 receptor agonist and D2 receptor antagonist, attenuates heroin self-administration and cue-induced reinstatement in rats.[Pubmed: 24145772] | 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.
METHODS AND RESULTS:
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.
CONCLUSIONS:
These results showed that L-SPD, which has dual actions on dopamine D1 and D2 receptors, attenuates heroin self-administration and cue-induced reinstatement. | | Neurobiol Aging. 2010 Jun;31(6):926-36. | | L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.[Pubmed: 18707801] | L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) remains a challenge in Parkinson's disease (PD) drug therapy.
METHODS AND RESULTS:
In the present study, we examined the effect of L-Stepholidine (L-SPD), a known dual dopamine receptor agent, on LID in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model. Daily administration of L-DOPA to PD rats for 22 days induced steady expression of LID, co-administration of L-Stepholidine with L-DOPA significantly ameliorated LID without compromising the therapeutic potency of L-DOPA, indicating that L-Stepholidine attenuated LID development. L-Stepholidine alone elicited stable contralateral rotational behavior without inducing significant dyskinesia. Acute administration of L-Stepholidine to rats with established LID produced significant relief of dyskinesia; this effect was mimicked by D(2) receptor antagonist haloperidol, but blunted by 5-HT(1A) receptor antagonist WAY100635. Furthermore, the mRNA level of 5-HT(1A) decreased significantly on 6-OHDA-lesioned striata, whereas chronic L-Stepholidine treatment restored 5-HT(1A) receptor mRNA level on the lesioned striata.
CONCLUSIONS:
The present data demonstrated that L-Stepholidine elicited antidyskinesia effects via both dopamine (D(2) receptor antagonistic activity) and nondopamine (5-HT(1A) agonistic activity) mechanisms. |
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