Reduced head-twitch response to quipazine of rats previously treated with methiothepin: possible involvement of dopaminergic system.

Methiothepin has been reported to induce an increase of specific binding sites for 3H-5TH 2-3 days following a single administration of a large dose. The present study was intended to ascertain whether methiothepin pretreatment would induce behavioral serotonergic supersensitivity, as assayed by evaluating head-twitch response to quipazine and L-5-hydroxytryptophan (L-5HTP). Methiothepin-pretreated rats exhibited a significantly reduced response after quipazine but not a significant change after L-5HTP. Such findings could be explained by considering that quipazine stimulates both serotonin and dopamine receptors and by hypothesizing that methiothepin also induced dopaminergic supersensitivity which hampered head-twitch behavior. Such an explanation was supported by the following findings. Rats tested 5 days after a large dose of haloperidol exhibited reduced head-twitch response to quipazine. Moreover, rats which had received a single administration of either haloperidol or methiothepin showed (1) more sustained spontaneous locomotor activity, and (2) enhanced stereotyped response to apomorphine.