Tolerance and crosstolerance to the suppressive effects of cocaine and morphine on lymphocyte proliferation.

The effects of acute or daily exposure to either cocaine or morphine on lymphocyte proliferative responses and NK cytolytic activity were determined. Two hours following the IV infusion of cocaine (5 mg/kg), blood lymphocyte proliferative responses were found to be suppressed by 75%. Cocaine had no effect on proliferative responses of thymic or splenic lymphocytes or cytolytic activity of splenic NK cells following acute or 5-day repetitive dosing. Similar to the effects of cocaine, morphine (10 mg/kg) administration was also accompanied by a suppressed blood lymphocyte response, which was no longer apparent 8 days following repeated morphine injections. Animals that had received daily injections of either morphine of cocaine were also found to be resistant to the inhibitory effects of a single dose of morphine or cocaine, respectively. These data suggest repeated exposure to either morphine or cocaine results in the development of an apparent crosstolerant state to further suppression of blood lymphocyte proliferative responses by either drug.