Environmental determinants of parachloroamphetamine toxicity in rats

The present investigation assessed PCA toxicity at 0.0, 5.0, and 10.0 mg/kg, in both social (4 rats per cage) and non-social (acrylic tube-restraint or tube restraint-plus-tail shock) circumstances with 16 rats per drug-environment condition. The results indicated that no dose of PCA alone yielded mortality under individual housing, and similarly no environmental circumstance by itself yielded mortality in the absence of PCA. However, various drug-environment interactions produced a dose-related enhancement of PCA toxicity. For both 5.0 mg/kg and 10 mg/kg parachloroamphetamine dose levels, restraint-plus-shock generated the highest percent mortality, followed by restraint-only, with conspecific aggregation producing a mortality incidence lower still. Further, the mortality displayed under each of these environmental conditions was greater for the 10.0 mg/kg PCA treatment than for the 5.0 mg/kg treatment. The results are discussed in terms of the relative aversiveness of the environmental setting and it is suggested that stress-related drug toxicity may be further analyzed in non-social settings. It is proposed that toxic environment-PCA interactions may result from altered cardiovascular and/or thermoregulatory processes, mediated by enhanced catecholaminergic activity.