Effects of Exercise Training on Behavior and Oxidative Stress in Diazepam Treated Rats.

Abstract

Diazepam (DZP) is an effective tranquilizing, due to its muscular relaxant and hypnotic properties. Reactive oxygen species (ROS) and other free radicals are produced during the cellular metabolism. Exercise training (ET) modulates positively oxidative stress, by improving antioxidant status (AO) and it could also modulate several functions of the central nervous system, such as behavior. PURPOSE: To investigate the influence of an eight week-exercise training protocol on locomotor behavior (LB) and systemic oxidative stress (OS) in rats treated chronically with DZP. METHODS: Thirty two male Wistar rats (160-180g) were assigned into four groups: sedentary control (SC), sedentary DZP (SD), trained control (TC) and trained DZP (TD). Diazepam, 5mg/kg i.p. was injected daily during eight weeks. ET consisted of running sessions on an adapted rodent treadmill, five times a week at 0.6-0.9Km/h and 0% grade, during 60min, through eight weeks. Exercise was performed at least 8h after drug administration. LB was assessed through the open field (OF) test. Systemic OS was evaluated in erythrocytes through lipid peroxidation (LPO) via a chemiluminescent technic (CL) and antioxidant enzyme activities of catalase (CAT) and glutahtione S-transferase (GST). The statistical package Graphpad was used RESULTS: TD animals presented an increase in CL (cps/mgHb) values (14,2 ± 0,5) when compared to SD (12.7 ± 0,3; p<0,05) and TC (11.3 ± 0.5 p<0,01) animals. CAT activity (pmol/mg prot) from TD group has also shown elevated values (35,0 ± 4,0) when compared to SD (22,4 ± 1.5; P< 0.05). Not only diazepam but also the exercise training protocol promoted an increase on GST activity, being SD (1.5 ± 0.1; P< 0.01) TC (1.3 ± 0.1; P< 0.05) and TD (1.7 ± 0.4 P< 0.001) when compared to SC (0.9 ± 0.08). DZP training animals showed higher total locomotion values (82,6 ± 4,9) than SD (54.5 ± 4.8) and TC (31.4 ± 6.2) animals. There was no association among the variables studied. CONCLUSIONS: DZP has induced an increase in oxidative damage and a consequent adaptation of the AO defenses, and the ET was not able to avoid these changes. Besides that, the locomotion capacity was not depressed by chconic DZP treatment, and the exercise training protocol significantly improved this values on DZP treated animals.