CHRONIC CADMIUM EXPOSURE ATTENUATES THE CONDITIONED REINFORCING PROPERTIES OF MORPHINE AND FENTANYL

Adult male rats were exposed ad libitum for 40 days to 100 ppm cadmium chloride through their diet, or an identical diet with no added cadmi um. Conditioned place preference (CPP) was conducted in a 2-chamber ap paratus in which all drugs were paired with the least-preferred side a s determined on a pre-test. In Experiment 1, control and cadmium-expos ed rats received 0, 0.6, 1.25, 2.5, or 5 mg/kg morphine sulfate (i.p.) for 4 days, and vehicle only for 4 days. Control animals showed a pre ference for the drug-paired side at 1.25, 2.5, and 5 mg/kg while the c admium-exposed rats showed a preference at 5 mg/kg only. In Experiment 2, rats were implanted with cannulae into the lateral ventricles and 0, 2, or 5 mu g morphine sulfate was administered intracerebroventricu larly (i.c.v.). An attenuation by cadmium again was observed, as contr ol animals showed a place preference at 2 and 5 mu g and cadmium-expos ed animals showed preference at 5 mu g only. In Experiment 3, increasi ng doses of the mu-opioid receptor agonist fentanyl (0, 0.0004, 0.004, and 0.04 mg/kg) were systemically administered (s.c.) and rats tested for CPP. While cadmium animals showed place preference only at 0.04 m /kg, control animals showed preference at 0.0004, 0.004, and 0.04 mg/k g. These findings are discussed within thr framework of metal-induced disturbance of neurochemical function and/or associative processing, a nd the implications that such disturbances may have for drug seeking a nd taking. (C) 1997 Elsevier Science B.V.