The effect of intraperitoneal administration of alpha-lipoic acid on locomotor activity impairment in the methamphetamine-induced neurotoxicity

Background and Aim: Methamphetamine is a potent psychostimulant with huge side effects. It was shown that acute exposure to methamphetamine induces oxidative stress in the brain and induces hyperactivity, anxiety and exploratory behaviors. Alpha Lipoic acid is made in animal body and is essential for aerobic metabolism. It acts as a potent antioxidant and scavengers free radicals. Methods: In this study male rats (۱۸۰-۲۲۰g) were used. Animals were divided into the following groups: Group ۱: control, group ۲: saline + saline, group ۳: saline (as methamphetamine solvent) + sunflower oil (as alpha-lipoic acid solvent), group ۴: methamphetamine + sunflower oil, group ۵: methamphetamine + alpha-lipoic acid ۱۰ mg/kg, group ۶: methamphetamine+alpha-lipoic acid ۴۰mg/kg. Rats received methamphetamine repeatedly (۲*۲۰ mg/kg, ½ hour interval). Alpha-lipoic acid was injected ۳۰ min, ۲۴ h and ۴۸ h after the last methamphetamine injection. At the third day, motor activity including movement, rearing, grooming, defecation, time spent at center zone, return to center and time spent in corner zones, were evaluated for ۲۰ minutes using open field apparatus. One-way ANOVA followed by LSD test was used for statistical analysis by SPSS software. Results: According to high consumption of methamphetamine, it is necessary to find new drugs or new methods for reducing its side effects. Therefore, in this study, the effect of intraperitoneal injection of alpha-lipoic acid, a potent antioxidant, on motor activity impairment induced by acute dose of methamphetamine, was investigated. Conclusion Our results showed that injection of alpha-lipoic acid significantly reduced the amount of displacement, defalcations, returning to the corner and peripheral zones. Alpha-lipoic acid also significantly increased the time spent at the center zone and the number of return to the center zone. Alpha-lipoic is essential for aerobic metabolism and also it exerts a strong antioxidant effect. Therefore, it seems that alpha-lipoic acid prevent neuronal damage in the brain nuclei such as accumbens or increases the activity of the histaminergic system, which play a major role in enhancing of motor activity by methamphetamine.

Keywords:

Methamphetamine , Alpha-lipoic acid , Oxidative stress , Open field