GENDER-RELATED DIFFERENCES IN COCAINE TOXICITY IN THE RAT

To test our hypotheses that gender-related differences in cocaine toxi city exist in the rat, cocaine (2 mg/kg/min) was infused intravenously in chronically catheterized male and ovariectomized or intact female rats until the onset of circulatory collapse. Sequential manifestation s of cocaine toxicity from mild central nervous stimulation to fatal c ardiovascular collapse were observed. Arterial blood was withdrawn at the onset of the toxic signs or symptoms for determination of cocaine concentrations. Dosages and plasma concentrations of cocaine required to produce cardiovascular toxic manifestations were significantly lowe r in male and ovariectomized rats than in intact females. Plasma choli nesterase activity was lowest in the male animals and highest in intac t females. These data suggest that systemic toxicity of cocaine is enh anced in male rats, because lower doses and plasma concentrations are required to induce toxic signs and symptoms.