ACUTE INFUSIONS OF COCAINE RESULT IN TIME-DEPENDENT AND DOSE-DEPENDENT EFFECTS ON LYMPHOCYTE-RESPONSES AND CORTICOSTERONE SECRETION IN RATS

In the present study, we investigated the effect of intravenously (i.v .) administered cocaine on mitogen-induced lymphocyte proliferation an d NK cytolytic activity in rats implanted with indwelling jugular cann ula. To assess whether the effects of cocaine were accompanied by adre nal gland activation, plasma corticosterone concentrations were also d etermined. It was found that the i.v. infusion of cocaine resulted in both a time- and dose-dependent decrease in both blood and splenic Con -A-stimulated lymphocyte proliferative responses. Within 60 minutes, b lood responses were maximally inhibited by more than 60% with 5 mg/kg cocaine. By 4 h, the suppression of blood lymphocyte responses was no longer significant. In contrast to these findings, there were no signi ficant effects observed with splenic lymphocyte responses until 4 h af ter drug administration. At this time, cocaine at doses of 5 and 10 mg /kg inhibited splenic proliferative responses by 50 and 75%, respectiv ely. These effects appeared to be selective, since no concurrent decre ases in NK cell activity were observed with 5 mg/kg at either 2 or 4 h . Within 30 min, plasma corticosterone concentrations were maximally i ncreased by 10-fold with 5 and 10 mg/kg doses of cocaine. At lower dos es of cocaine (1 mg/kg), neither changes in lymphocyte proliferative r esponses, NK cytolytic activity nor plasma corticosterone levels were apparent. This study demonstrates that a single i.v. infusion of cocai ne results in a selective dose- and time-dependent immunosuppression w hich is preceded by transient increases in circulating levels of corti costerone.