Cocaine toxicity: genetic differences in cocaine-induced lethality in rats

Cocaine produces stimulation, depression, convulsions and death, and binds at several receptor sites. Thus cocaine may produce toxicity through similar or distinct pathways from those associated with stimulation. Genetic differences in stimulant response to cocaine have recently been reported for four inbred rat strains, ACI, F344, LEW and NBR. In the present study, significant genetic differences were found in cocaine-induced lethality, with a two-fold difference in LD50 values seen between the most sensitive (NBR) and least sensitive (LEW) strains. Sensitivity to lethality was not correlated with sensitivity to stimulation, but was highly correlated with baseline activity. This lack of strong association between stimulant and lethal effects of cocaine may be important in clinical manifestations of the cocaine sudden death syndrome.