Effects of (-)stepholidine in animal models for schizophrenia.

OBJECTIVE

(-)Stepholidine (SPD) is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D(1) and D(2) like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1) and a D(2) antagonist, which could make SPD a unique antipsychotic drug. The present study aimed to investigate the antipsychotic properties of SPD in two animal models for schizophrenia.

METHODS

The effects of SPD, clozapine and haloperidol in increasing forelimb and hindlimb retraction time in the paw test and in reversing the apomorphine and MK801-induced disruption of prepulse inhibition was investigated.

RESULTS

In the paw test, clozapine and SPD increased the hindlimb retraction time, with only a marginal effect on the forelimb retraction time, whereas haloperidol potently increased both. In the prepulse inhibition paradigm, all three drugs reverse the apomorphine-induced disruption in prepulse inhibition, while none of the drugs could reverse the MK801-induced disruption. SPD even slightly, but significantly, potentiated the effects of MK801.

CONCLUSIONS

The data show that SPD showed antipsychotic-like effects in both the prepulse inhibition paradigm and in the paw test. Moreover, the results of the paw test suggest that SPD has an atypical character with a relatively small potency to induce extrapyramidal side effects.