Exercise modifies amphetamine relapse: Behavioral and oxidative markers in rats

•Rats developed preference and relapse to amphetamine (AMPH).•AMPH increased intensified anxiety-like symptoms related to abstinence.•AMPH increased oxidative damages and modified enzymes activity in hippocampus.•Exercise reduced AMPH-relapse and anxiety-like symptoms after re-exposure to drug.•Exercise increased enzymes activity and prevented oxidative damages in hippocampus.

Exercise has been reported to attenuate rewarding symptoms related to addictive drugs mainly by affecting the brain neuroplasticity and neurotransmission. In this study, we investigated the influence of physical exercise on the behavioral and enzymatic status related to drug relapse in rats. Animals were primarily treated with amphetamine (AMPH; 4.0 mg/kg, i.p.) or vehicle (C; NaCl 0.9% solution) in the conditioned place preference (CPP) paradigm for 14 days. Half of each experimental group was then submitted to swimming sessions (60 min/day, 5 days/week) for 5 weeks. Animals were re-exposed to AMPH- or vehicle-CPP paradigm for another 3 days, in order to observe drug relapse and anxiety-like symptoms, which were observed 24 h after AMPH reconditioning in CPP, and elevated plus maze (EPM), respectively, and brain biochemical evaluations were carried out subsequently. While AMPH was related to place preference and anxiety, indicating drug addiction and abstinence symptoms, respectively, physical activity was able to prevent relapse symptoms after AMPH reconditioning, as observed through consecutive decreased CPP and anxiety-like symptoms. In addition, AMPH exposure increased reactive species (RS) generation and protein carbonyl (PC) levels together with decreased activity of catalase- and Na+K+-ATPase in hippocampus. On the other hand, while all AMPH-induced effects were prevented by physical activity, there was a negative correlation between PC levels (r = 0.65; p < 0.003) and CAT activity, and a positive correlation between RS generation and PC levels (r = 0.54; r = 0.52, p < 0.05) with AMPH–CPP after exercise. These results indicate that exercise has a clear beneficial influence on the prevention of psychostimulant drug relapse.