The effect of cadmium on tolerance induction to analgesic effects of morphine in rats

Cadmium element is found in all of tobacco products such as cigarette. There is some evidence that indicate cadmium may interfere with morphine tolerance development. The effect of cadmium on morphine tolerance development and its possible cross tolerance were investigated in this study. To induce tolerance to analgesic effect of morphine or cadmium, morphine (15 µg/rat) or cadmium (20 nmol/rat) were injected intrathecally to male rats twice a day for five days. To investigate the effect of cadmium on morphine tolerance, another group of rats were injected intrathecally with cadmium and morphine. Cadmium was applied 15 minutes prior to morphine administration. The analgesic effect of different treatments was measured using tail flick test. The results indicated a long lasting analgesic effect of cadmium which was obvious after 12 hours. Repetitive administration of cadmium caused tolerance development to its analgesic effect. In animals which received cadmium during first 5 days, morphine could not induce a significant analgesia on day 6 (cross tolerance). The comparison of the tail flick latencies in morphine and cadmium+morphine treated groups, did not show a significant difference, indicated that cadmium did not have any inhibitory effect on development of morphine tolerance. Our results showed that intrathecal administration of cadmium causes cross-tolerance to analgesic effect of morphine. It seems that, cadmium of cigarettes which induces analgesia by itself causes morphine tolerance and develops some aspect of morphine addiction.