Comparative studies of sulpiride and classical neuroleptics on induction of catalepsy, locomotor activity, and brain dopamine metabolism in mice.
The effects of the peripheral administration of sulpiride on the induction of catalepsy, the vertical (VMA) and horizontal (HMA) locomotor activities, and on the dopamine metabolism in the limbic system, striatum, and nucleus accumbens were examined using mice up to 7.5 h after administration of drugs. These effects were compared to those of pimozide and haloperidol. Sulpiride (1.25-160 mg/kg, IP) clearly induced catalepsy similar to pimozide (0.0625-4 mg/kg, IP) and haloperidol (0.0375-0.3 mg/kg, IP). During the induction of catalepsy, the intensity was the strongest at 4.5 h after administration and the ED50 value showed 11.5 mg/kg at that time. However, a moderate dose of sulpiride at 10-20 mg/kg did not show the induction of a dose- and time-dependent catalepsy. During the locomotor activity, the VMA was significantly inhibited at 1.5 h and 6 h after administration of pimozide (0.25 mg/kg, IP) and haloperidol (0.075 mg/kg, IP) as compared to the control group, while the HMA was significantly inhibited at 1.5 h after administration of sulpiride (40 mg/kg, IP) and pimozide (0.25 mg/kg, IP). Subsequently, in the dopamine metabolism, sulpiride, pimozide, and haloperidol: 1) considerably accelerated the turnover in the dopamine metabolism in three distinct brain areas; 2) increased the levels of the DOPAC, HVA, and 3-MT even 6 h after administration, as well as at 1.5 h after administration; and 3) decreased the levels of dopamine in the nucleus accumbens at 1.5 h after administration. These results indicate that sulpiride displays a mode of action different from pimozide and haloperidol with regard to the induction of catalepsy, but not with regard to the locomotion and brain dopamine metabolism.
Department of Pharmacology, School of Dentistry, Iwate Medical University, Morioka, Japan.
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Fujiwara
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002375:Catalepsy / Q000188:drug therapy*; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010868:Pimozide / Q000008:administration & dosage / Q000494:pharmacology; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology*
D014150:Antipsychotic Agents; D010868:Pimozide; D013469:Sulpiride; D006220:Haloperidol; D004298:Dopamine