Effects of haloperidol on MK-801-induced hyperlocomotion and deficits of prepulse inhibition in mice.

Objective To investigate the effects of haloperidol on hyperlocomotion and deficient prepulse inhibition(PPI) in MK-801 induced hypoglutamatergic schizophrenia model in mice.Methods One hundred fifty-two male Kunming mice were assigned randomly to different groups(n=8 or n=10).MK-801 at 0.25 mg/kg or 0.5 mg/kg was used to induce hyperlocomotion or deficient PPI.Effects of haloperidol(0.03,0.1 and 0.3 mg/kg) on explorative behavior,spontaneous locomotion,MK-801-induced hyperactivity and were examined.Effects of haloperidol(0.1,0.3,1 mg/kg) on intact and MK-801-disrupted PPI were examined.Results Haloperidol(0.1 and 0.3 mg/kg) significantly inhibited the explorative behavior and spontaneous locomotion(P0.05).Haloperidol at 0.03 mg/kg had no effect on exploration and spontaneous activity(P0.05).Haloperidol(0.1~0.3 mg/kg) dose-dependently antagonized MK-801-induced hyperlocomotion(F=27.23,P0.01),resulting in 22% and 65% reduction in total distance when administered at 0.1 and 0.3 mg/kg,respectively(P0.01).Haloperidol(0.1~1mg/kg) dose-dependently enhanced baseline PPI(F=9.06,P0.001),resulting in 44%,60% and 61% increase when administered at 0.1,0.3 and 1 mg/kg(P0.05),respectively.Only the highest dose of Haloperidol(1mg/kg) diminished MK-801-induced disruption of PPI(P0.05).Conclusions Haloperidol non-specifically inhibits the MK-801-induced hyperlocomotion and disruption of PPI.