Effects of restraint and animal interaction on carbon monoxide lethality: Stress and the role of corticosterone

JB Larsen
KT Fokakis
MA Massett
LA Ciccarelli


Stress is known to alter physiological homeostasis and distort experimental results. In particular, stress associated with restraint and group-interaction may modify the lethality of toxic substances, Median lethal concentrations (LC50) for carbon monoxide (CO) were determined using restrained or unrestrained mice exposed for 30 min as groups or individuals. To evaluate stress levels, the serum concentration of corticosterone (COS) was determined for each exposure configuration by radioimmunoassay. Additional LC50 values for CO were determined after treating groups of restrained mice with mifepristone (10 mg/kg), to block the effects of COS, and groups of unrestrained mice with exogenous COS (2 mg/kg), to elevated the serum level. The LC50 value obtained using restrained mice exposed in groups (0.26%) was significantly lower (p < 0.05) than the values derived from all other exposure configurations (0.41-0.58%). The higher LC50 values did not differ significantly, although the highest values were obtained from individual exposures. Levels of COS were strongly correlated with CO toxicity (r = 0.90), The LC50 obtained from mifepristone-treated mice (0.41%) was significantly higher (p < 0.05) than that obtained from restrained groups of untreated mice (0.26%), However, treatment with COS did not alter the LC50 obtained from unrestrained groups of mice (0.41%). The results suggest that restraint and interaction must be coupled to significantly modify estimates of toxicity, and that effective interaction between restrained mice can occur (probably mediated by olfactory cues). Both factors appear to elevate stress levels in mice, and stress appears to increase the sensitivity of mice to intoxication by CO. However, COS may not be entirely responsible for the effects of stressors on toxicity, Copyright (C) 2000 John Wiley & Sons Ltd.