Modulation of Lipid Peroxidation in the Brain and Liver as a Possible Mechanism for the Protective Effect of Melatonin in Drug Addiction

Sergey Pertsov

Pertsov, Sergey P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences

An impressive body of evidence indicates that drug abuse is accompanied by pathological changes in the central nervous system, variations in the intensity of free radical lipid peroxidation, and progression of acute or chronic stress. A relationship was revealed between the stress response and intensity of lipid peroxidation. The severity of disorders differs in various individuals and depends on predisposition to the development of drug addiction. The pineal hormone, melatonin, possesses biorhythmic, antioxidant, immunomodulatory, and stress-protective properties. Our previous studies and published data show that melatonin may be used for correcting disturbances resulting from phase shifts in circadian rhythms in drug abusers. This work was designed to study the effects of acute stress and exogenous melatonin on the intensity of lipid peroxidation in the brain and liver of rats with different activity in the open field. We also monitored the changes in plasma melatonin levels observed after melatonin administration and stress. Experiments were performed on 80 male Wistar rats. Depending on the open-field behavior, the animals were divided into groups of behaviorally active (n=34) and passive animals (n=46). Previously, we revealed that active rats are resistant, while passive animals are predisposed to the development of drug addiction. Melatonin in doses of 0.5, 1, and 2 mg/kg, or physiological saline, was injected intraperitoneally immediately before stress. Control animals received similar injections, but were not stressed. Acute stress was produced as described by Overmier et al., 1986. The rats were immobilized in plastic tubes and immersed in water for 2 hours, then they were returned to home cages for another 2 hours (post-stress period). After the experiment, the rats were euthanized. We measured the content of malonic dialdehyde (end product of lipid peroxidation) in emotiogenic structures of the brain involved in the development of drug addiction and stress response (hypothalamus and sensorimotor cortex). Besides this, malonic dialdehyde content was estimated in the liver, characterized by most pronounced structural and functional changes in drug abusers. Plasma melatonin concentration was assayed radioimmunologically withH3-labeled melatonin. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. No changes were revealed in plasma melatonin concentrations in stressed animals injected with physiological saline. Exogenous melatonin increased plasma melatonin concentration, both in active and passive rats, under normal conditions and after stress. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. Our results indicate that the protective effects of melatonin in drug abusers are partly related to modulation (sometimes activation) of lipid peroxidation in central and peripheral tissues of the organism.

Abstract Year: 
2005
Abstract Region: 
Central Asia
Abstract Country: 
Russian Federation
Abstract Category: 
Basic Science