Evaluation of the Effects of Ketorolac on Tolerance and Dependence to Morphine in Male Mice

According to the high prevalence of pathologic and physiologic dependence to morphine as a strong opioid analgesics and tolerance to analgesic effects, it seems inevitable to find solutions to reduce these consequences. Previous studies addressed different types of drugs, such as anti-seizure drugs and anti-psychotics. This study aimed to investigate the effects of ketorolac on tolerance and dependence to the analgesic properties of the chronic use of morphine in male mice.   In this study, adult male albino mice were divided into 9 groups. In order to investigate the analgesic tolerance, mice received morphine plus ketorolac either on 5 consecutive days or a single dose in the fifth day. The hot plate test was performed and latency times were recorded. For the evaluation of chemical pain, formalin subplantar injection was administered and the pain marks were recorded. Finally, dependence assessment was performed using naloxone hydrochloride injection on the fifth day, and the withdrawal symptoms were recorded.   There was a significant difference (P<0.05) among the single dose of morphine, normal saline (as the negative control group), and chronic morphine administration; with no significant difference between taking a single dose of morphine or ketorolac in the addicted mice. Regarding the dependence, there was a significant difference (P<0.05) between the chronic use of morphine and chronic morphine plus ketorolac administration were reported.   It can be concluded that ketorolac have an anti-analgesic effect on chemical pain. It reduces tolerance to morphine anti-analgesic effect and it is capable of reducing the withdrawal syndrome symptoms induced by naloxone.