BRAIN AND PLASMA-LEVELS OF COCAINE AND BENZOYLECGONINE IN LEAD-EXPOSED AND CADMIUM-EXPOSED RATS FOLLOWING ACUTE OR CHRONIC INTRAPERITONEAL ADMINISTRATION OF COCAINE

Previous investigations of metal/cocaine interactions have shown that chronic oral exposure to inorganic lead or cadmium attenuates the psyc hoactive effects of acute or repeated administration of cocaine. The p urpose of this investigation was to assess the possibility that such i nteractive effects may derive from metal-induced disturbances in cocai ne pharmacokinetics, i.e., delivery of cocaine to critical biologic si tes may be disrupted by metal contamination. In this study, adult male rats were exposed to purified diets containing 250 ppm lead acetate ( Group Lead), 100 ppm cadmium chloride (Group Cadmium), or unadulterate d laboratory chow (Group Control); n = 48/exposure condition. Followin g ad libitum access to their respective diets in the home cage for 45 days, half the animals from each exposure regimen received single dail y LP injections of 5, 10, or 20 mg/kg cocaine HCl for a period of 7 da ys (n = 8/group). The remaining half the animals received repeated dai ly injections of saline during this pretreatment phase. On the day fol lowing pretreatment, animals previously receiving cocaine injections w ere administered a single cocaine test challenge at a dose equal to th at received in pretreatment. Similarly, saline pretreatment animals re ceived either 5, 10, or 20 mg/kg cocaine. The results of this investig ation did not reveal reliable evidence of metal-related differences in brain levels of cocaine. Plasma cocaine and benzoylecgonine (BE) leve ls also were essentially the same for control and metal-exposed animal s. The failure to show that lead or cadmium alters the disposition of cocaine in brain or plasma underscores the need to pursue alternative accounts of metal/cocaine interactions. (C) 1997 Elsevier Science Irel and Ltd.