EFFECTS OF CARAMIPHEN AND PHENCYCLIDINE ALONE AND IN COMBINATION ON BEHAVIOR IN THE RAT

Because dextromethorphan (DM) has been shown to inhibit the locomotor stimulant effects of phencyclidine (PCP), this study explored further the possible interaction between drugs acting on DM and PCP receptor s ites. Caramiphen, an antitussive that binds with high affinity to the DM site, was injected (IF) alone (15-120 mg/kg) or at two doses (15 or 60 mg/kg) 15 min before a challenge dose of PCP (1.25-20 mg/kg). Cara miphen alone dose-dependently increased ataxia, increased stereotypy, and had no effect on locomotor activity. PCP alone dose-dependently in creased ataxia, stereotypy, and locomotor activity, the latter showing an inverted U-shaped function. At both pretreatment doses, caramiphen enhanced locomotor activity and stereotypy when combined with low PCP doses but decreased these behaviors at high PCP doses. Caramiphen pro duced a dose-dependent additive effect on ataxia when combined with al l PCP doses. It was concluded that, although caramiphen, like DM, inhi bited the locomotor stimulant effects of selected doses of PCP, that i nteraction appeared to be due to other behaviors (e.g., ataxia/stereot ypy) elicited by caramiphen combined with high doses of PCP. This stud y underscored the importance of using full dose ranges of PCP when att empting to antagonize its behavioral effects with other drugs.