POTENTIATION OF L-DOPA-INDUCED BEHAVIORAL EXCITEMENT BY HISTAMINE H-1-RECEPTOR ANTAGONISTS IN MICE

Effects of histamine H-1-receptor antagonists on L-dopa-induced behavi oral excitement were examined in mice to confirm behaviorally the inhi bition of dopamine uptake by these compounds. L-Dopa (100-300 mg/kg, s .c.) combined with pargyline hydrochloride (80 mg/kg, i.p.) caused a d ose-dependent behavioral excitement. The marked excitement induced by L-dopa (300 mg/kg) plus pargyline was significantly inhibited by pimoz ide (0.1-1 mg/kg, s.c.), a selective dopamine antagonist. Tripelennami ne (10 mg/kg, s.c.), d-chlorpheniramine (1 and 2 mg/kg, s.c.), homochl orcyclizine (2 and 5 mg/kg, s.c.), diphenhydramine (2 and 5 mg/kg, s.c .) and mepyramine (2 and 5 mg/kg, s.c.) each markedly enhanced the mod erate behavioral excitement induced by L-dopa (150 mg/kg) plus pargyli ne. These findings are behavioral evidence for inhibition of dopamine uptake by H-1 antagonists, which has been suggested by neurochemical s tudies.