A time-activity baseline to measure pharmacological and non-pharmacological manipulations of PCP-induced activity in mice.

Abstract

At critical doses of PCP (10 mg/kg i.p. in the present studies), locomotor stimulation in mice is initially suppressed by short-lasting ataxia, albeit at higher levels of activity than controls. This provides a time-activity baseline of PCP-stimulated locomotion potentially sensitive 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 similar to that seen at higher PCP doses and iii) reductions in activity without a change in the time-activity relationship. This baseline was explored using three manipulations employed in the clinical management of PCP toxicity: treatment with a neuroleptic (haloperidol), a benzodiazepine (chlordiazepoxide) and modification in environmental stimulation (changing of lighting conditions). Both haloperidol (0.125-0.5 mg/ kg, i.p.) and chlordiazepoxide (5-20 mg/kg i.p.) further reduced activity during the ataxic phase of the PCP time-activity relationship qualitatively similar to the effects of pentobarbital (20-40 mg/kg i.p.). Changing of lighting conditions from red to white light resulted in significant reductions in levels of activity of PCP-treated animals but no change in the time-activity relationship. No manipulation resulted in true reversal of the PCP induced time-activity relationship. The results parallel the clinical findings that neuroleptic and benzodiazepine administration have no specific effects upon PCP-intoxication and that environmental manipulation may modify the degree of PCP stimulation. The time-activity baseline described may prove useful in the evaluation of the effects of pharmacological and non-pharmacological manipulations of PCP-induced activity in rodents.