Antagonism of morphine-induced antinociception by tetrandrine is dependent on serotonergic mechanisms

'Tetrandrine (TET), a non-specific calcium antagonist, inhibited morphine-induced antinociception in the tail-flick test in mice. This study was undertaken to assess the mechanism of the antagonism of morphine-induced antinociception by TET. Morphine-induced antinociception was prevented by pretreatment with TET in the tail-flick but not in the tail-pinch tests carried out in mice and this antagonism was abolished by pretreatment of a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not by the pretreatment of a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA), in the tail-flick test. These results indicate that serotonergic mechanisms are involved in the antagonism of morphine-induced antinociception by TET. On the other hand, the development of morphine-induced analgesic tolerance was not prevented by TET. This result, in agreement with other reports, also indicates the possible dissociation of morphine analgesic effect from its tolerance-inducing effect. In addition, TET suppressed the 5-hydroxytryptamine (5-HT)-induced head twtch response. This result provides additional evidence that TET may modulate serotonergic function and the antagonism of morphine-induced antinociception by TET is dependent on serotonergic mechanisms.