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.
Dall'Olio
R
R
Vaccheri
A
A
Montanaro
N
N
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D003988:Dibenzothiepins / Q000494:pharmacology*; D006220:Haloperidol / Q000008:administration & dosage; D006257:Head; D008297:Male; D008719:Methiothepin / Q000494:pharmacology*; D009068:Movement / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D003988:Dibenzothiepins; D011804:Quinolines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D011814:Quipazine; D008719:Methiothepin; D006916:5-Hydroxytryptophan; D006220:Haloperidol