A TIME-ACTIVITY BASE-LINE TO MEASURE PHARMACOLOGICAL AND NONPHARMACOLOGICAL MANIPULATIONS OF PCP-INDUCED ACTIVITY IN MICE

At critical doses of PCP (10 mg/kg IP in the present studies), locomot or stimulation in mice ij initially suppressed by short-lasting ataxia , albeit at higher levels of activity than controls. This provides a t ime-activity baseline of PCP-stimulated locomotion potentially sensiti ve to i) pharmacological antagonism indicated by a change in the time- activity relationship to that seen at lower PCP doses, ii) interaction with the ataxic phase resulting in further decreases in activity simi lar to that seen at higher PCP doses and iii) reductions in activity w ithout a change in the time-activity relationship. This baseline was e xplored using three manipulations employed in the clinical management of PCP toxicity: treatment with a neuroleptic (haloperidol), a benzodi azepine (chlordiazepoxide) and modification in environmental stimulati on (changing of lighting conditions). Both haloperidol (0.125-0.5 mg/ kg, IP) and chlordiazepoxide (5-20 mg/kg IP) further reduced activity during the ataxic phase of the PCP time-activity relationship qualitat ively similar to the effects of pentobarbital (20-40 mg/kg IP). Changi ng of lighting conditions from red to white light resulted in signific ant reductions in levels of activity of PCP-treated animals but no cha nge in the time-activity relationship. No manipulation resulted in tru e reversal of the PCP induced time-activity relationship. The results parallel the clinical findings that neuroleptic and benzodiazepine adm inistration have no specific effects upon PCP-intoxication and that en vironmental manipulation may modify the degree of PCP stimulation. The time-activity baseline described may prove useful in the evaluation o f the effects of pharmacological and nonpharmacological manipulations of PCP-induced activity in rodents.