Cahill-Morasco_1998_J.Toxicol.Clin.Toxicol_36_667

BACKGROUND Low plasma cholinesterase activity is associated with severe cocaine toxicity in human subjects and animal experiments. Exogenously enhanced plasma cholinesterase activity is protective against cocaine toxicity in animals. Cocaine users tend to have lower plasma cholinesterase activity than controls. Yet, when cocaine users are allowed to use cocaine in controlled settings without dietary restriction, their plasma cholinesterase activity increases. This study evaluates the influence of diet on plasma cholinesterase activity and cocaine toxicity. METHODS: Forty-five Swiss albino mice were maintained on a high (30%) protein diet for 3 weeks. They were then randomized into equal groups and given either the high protein diet, an isocaloric low protein diet, or a protein and calorie deficient diet which consisted of reduced intake of the high protein diet. Body weights and plasma cholinesterase activities were measured after a 21-day study period. All animals then received a fixed dose of intraperitoneal cocaine and were observed for seizures and death. RESULTS: Body weights and plasma cholinesterase activities of the high protein animals remained stable. Weights for the low protein and reduced intake animals fell by 5% and 15%, respectively (p < 0.05 for both vs baseline). Similarly, plasma cholinesterase activities for the low protein and reduced intake animals fell by 4% and 10%, respectively (p = 0.06 for low protein and < 0.05 for reduced intake vs baseline). Cocaine caused seizures in 67% of the high protein animals as compared to 93% and 100% of the low protein and reduced intake animals, respectively (p < 0.05 for high protein vs reduced intake). None of the high protein animals died as compared to 20% and 100% of the low protein and reduced intake animals, respectively (p < 0.05 for high protein vs reduced intake). CONCLUSION: Protein and calorie malnutrition is associated with a reduction in plasma cholinesterase activity and enhanced cocaine toxicity in mice. Further study is needed to determine if dietary factors are partially responsible for variations in plasma cholinesterase activity and cocaine susceptibility in humans.