Morphine or its withdrawal affects plasma malondialdehyde, vitamin E levels and absence or presence of abstinence signs in rats

Objectives: Various experimental observations show that morphine treatment generates reactive oxygen species, and that its discontinuation leads to signs of withdrawal. We therefore investigated plasma malondialdehyde and vitamin E levels under both conditions to verify the occurrence of any alterations in oxidative metabolism, and whether these are associated with behavioural changes. Methods: We investigated the effects of morphine or morphine plus naloxone on plasma malondialdehyde, vitamin E levels and withdrawal signs such as jumping, wet dog shakes and faecal excretion in rats. Furthermore, isopropylnoradrenaline was injected in rabbits to verify its effects on plasma malondialdehyde levels. Key findings: Morphine treatment increased free malondialdehyde and decreased vitamin E levels. The elevation in malondialdehyde levels were exacerbated by the abrupt removal of morphine by naloxone, which also led to the appearance of withdrawal signs. The increased malondialdehyde values can be attributed to the interactions of reactive oxygen species with unsaturated fatty acids, and the lowered levels of vitamin E to its interactions with reactive oxygen species. Conclusions: A connection seems to exist between altered peroxide status and withdrawal signs in abstinent animals.