Abstract
Chronic exposure to the toxicant cadmium has been shown to produce an attenuation in behavior properties of drugs of abuse. The experiments presented examined the effects of cadmium on the conditioned reinforcing properties of morphine and fentanyl using the conditioned place preference paradigm (CPP). In CPP a drug is repeatedly paired with a neutral stimulus. When given free-choice access, the animal spends more time in the drugpaired rather than a non-drug-paired environment. In these experiments 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 cadmium. CPP was conducted in a 2-chamber apparatus in which all drugs were paired with the least-preferred side as determined on a pre-test. In Experiment 1. control and cadmium-exposed rats received 0, 0.6, 1.25, 2.5. or 5 mg/kg morphine sulfate (ip) for 4 days, and vehicle only for 4 days. Control animals showed a preference for the drug-paired side at 1.25, 2.5. and 5 mg/kg while the cadmium-exposed rats showed a preference at 5 mg/kg only. In Experiment 2. rats were implanted with cannulae into the lateral ventricles and or 5 morphine sulfate was administered intracerebroventricularly (icv) to determine whether the results seen in Experiment 1 were due to an antagonsim by cadmium in the periphery rather than the CNS. An attenuation by cadmium again was observed, as control animals showed a place preference at 2 and 5 @g and cadmium-exposed animals showed preference at 5 jig only. In Experiment 3, increasing doses of the selective g- opioidreceptor agonist fentanyl (0, 0.0004, 0.004, and 0.04 mg/kg)were systemically administered (sc) and rats tested for CPP. While cadmium animals showed place preference only at 0.04 mg/kg, control animals showed preference at 0.0004, 0.004, and 0.04 mg/kg. These results point to an attenuation rather than a suppression of the conditioned reinforcing properties of the opiates.
Miller, Dennis K (1997). Effects of chronic cadmium exposure on the conditioned reinforcing properties of morphine and fentanyl in rats. Master's thesis, Texas A&M University. Available electronically from
https : / /hdl .handle .net /1969 .1 /ETD -TAMU -1997 -THESIS -M547.