THE EFFECTS OF COCAINE INJECTIONS ON MOUSE THYMOCYTE POPULATION

C57 BL mice were injected daily with either saline or varied doses of cocaine (5-50 mg/kg), and thymocyte subpopulations were analyzed 4 hr after the fifth injection, Mice injected with either 25 or 50 mg/kg of cocaine showed a decrease in the percentage of CD4(+)8(+) cells and i ncrease of CD4(-)8(-), CD4(+), and CD8(+) cells. The absolute numbers of each subpopulation, calculated by multiplying the percentage of eac h subpopulation with the total cell number, revealed an extensive decl ine in CD4(+)8(+), a decrease in CD8(+), an increase in CD4(-)8(-), an d no change in the CD4(+) subpopulation. Flow cytometric analysis of t hymocytes and electrophoresis of the thymocyte DNA revealed a dosage-d ependent increase in cells undergoing programed cell death with apopto sis. Culturing of thymocytes from control or drug-treated mice demonst rated an inverse relationship between cell viability and cocaine conce ntrations, suggesting that in vivo cocaine, or its biological products , may damage thymocytes, Incubation of normal cells with cocaine showe d a dose-dependent decrease of viability with identical patterns of th e alteration of cell subpopulations observed in vivo. A dose-dependent increase of apoptosis was also observed, In summary, we demonstrate a selective in vivo cocaine-induced alteration of the thymocyte subpopu lations and identified programed cell death with apoptosis as the like ly mechanism mediating this thymic atrophy, The comparable findings ob served in vivo and in vitro support the concept that cocaine may direc tly affect some features of thymocyte biology, and suggest the usefuln ess of the in vitro system in studying cocaine effects on thymocyte bi ology.