Interactions between phencyclidine and central nervous system depressants evaluated in mice and rats

The effects of phencyclidine (PCP) alone and in combination with the CNS depressants, pentobarbital (PB) or ethanol (ETOH), were determined in mice using the inverted screen test and in rats using disruption of milk drinking behavior. The effects of PB and ETOH alone, and in combination, were also determined so that the PCP combinations could be compared to this clinically relevant interaction. These homergic drug interactions were analyzed using the dose-addition model by isobolographic analyses. Most drug combinations resulted in shifts to the left of the dose-effect curves relative to the dose-effect curves for the drugs alone; in no cases were shifts to the right (antagonism) observed. In general, the interactions between PCP and ETOH or PB were quantitatively less (infra-additive) than the interaction between the CNS depressants (dose-additive) when studied in mice. In the rat studies, the interactions between PCP and ETOH or PB were, overall, quantitatively greater (dose-additive or supra-additive) than the ETOH-PB interactions (infra-additive). Since even infra-additive interactions may result in substantially enhanced effects, these results suggest that coabuse of PCP with CNS depressant drugs could produce marked behavioral toxicity.