Dietary cadmium exposure alters characteristics of training, substitution,and tolerance when morphine is used as a discriminative stimulus

This study examined the possibility that cadmium, a toxicant in high concen tration in all tobacco products, may alter the stimulus properties of morph ine. Adult male rats were exposed to regular laboratory chow (Group Control ) or chow containing 100 ppm added cadmium chloride (Group Cadmium). Follow ing an initial 30 day exposure period, control and cadmium-exposed animals were trained to discriminate between i.p. injections of 3.00 mg/kg morphine sulfate and vehicle (distilled water) in a two-choice drug discrimination task. Subsequently, the morphine dose-effect generalization function (0.75- 6.00 mg/kg) was determined for control and cadmium-exposed animals. Additio nal substitution tests were conducted with increasing doses of the high eff icacy mu agonist fentanyl (0.0016-0.04 mg/kg), the intermediate efficacy mu agonist (-)-metazocine (0.60-5.00 mg/kg) and the kappa agonist (+/-)-brema zocine (0.03-0.12 mg/kg). Also, increasing doses of the selective mu antago nist naloxone (0.0008-0.50 mg/kg) were presented against the training dose of morphine (3.00 mg/kg) and 0.02 mg/kg fentanyl. Finally, training was dis continued, and control and cadmium-exposed animals were injected with 8.00 mg/kg morphine in the home cage every 12 hr for 2 weeks, prior to redetermi ning the morphine dose effect function. Following a 1 week recovery period where morphine injections were discontinued, a final determination of the m orphine dose-effect function was made. The results of the investigation ind icated that cadmium exposure, without affecting the rate-changing propertie s of the drugs, slowed initial acquisition of the morphine discrimination, decreased the potency of selective doses of naloxone with respect to antago nizing the stimulus effects of morphine and fentanyl, and blocked the devel opment of tolerance to morphine. Morphine, fentanyl, and (-)-metazocine gen eralized (substituted) equally across both groups, while (+/-)-bremazocine failed to substitute for the morphine stimulus in either group. These findi ngs add to the growing literature on the interaction between metal poisonin g and drug selection/abuse. (C) 2000 Intox Press, Inc.