Effect of copper status on acute toxicity of cocaine in rats

Both copper (Cu) nutriture and cocaine (Coc) ingestion have been shown to affect cardiovascular integrity. Therefore, the purpose of these studies was to determine if Cu status affects the acute toxicity of Coc. 20 weanling male rats (45 {plus minus} 5 g) were randomly assigned to 2 groups, 1 fed a copper deficient (CuD) (<1ppmCu) and the other a copper supplemented (CuS) diet (ca.6ppm, Cu). After 7 wks, the rats, paired for Cu status, were injected (ip) with Coc-HCl at reported LD{sub 50} doses ranging from 80-90 mg/kg bw. The CuD was established by cardiac hypertrophy, depressed hematocrit, lowered serum, liver and heart Cu compared to the CuS controls. The acute toxicity resulted in tachycardia and hyperactivity followed by ataxia with isolated muscle twitchings and violent grand-mal type seizures. For those animals that died, death was apparently due to respiratory arrest followed by ventricular fibrillation; animals that survived were killed by exsanguination. The severity of toxicity was greater for the CuD rats as evidenced by 100% exhibiting seizures compared to 80% for the CuS group. In addition, the incidence of death was 60% for the CuD group compared to 20% for the CuS rats. Although these results suggest that CuDmore » exacerbates the toxic effects of Coc, it is not established that the effects are specific for this essential nutrient.« less