Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats

Forced exercise can alleviate cognitive-behavioral deficits in an experimental model of addiction. However, the effects of different intensities of forced exercise in improving behavioral, cognitive and biochemical deficits during morphine abstinence period are not well investigated. Thus, the current work examined the effects of different loads of forced exercise on cognition functions, anxiety behavior and BDNF changes in the hippocampus, and prefrontal cortex (PFC), and also serum levels of BDNF and corticosterone during the abstinent period in male rats. Animals received morphine injections (10 mg/kg, twice a day) for 10 consecutive days. Then, the animals were exposed to a 4-week forced exercise training program under low, moderate or high intensities (30 min per session on 5 days a week), which accompanied by behavioral and biochemical tests. In Experiment 1, anxiety-like behaviors using elevated plus maze (EPM), and light/dark box (L/D box) were examined. In Experiment 2, cognitive functions using T-maze alteration and passive avoidance tasks were tested, which accompanied by BDNF measurements in the hippocampus and PFC. In Experiment 3, serum levels of BDNF and corticosterone following the termination of forced exercise regimen were measured. Morphine-abstinent animals exhibited anxiogenic -like behaviors in the EPM, but not L/D box. They also exhibited impaired T-maze alternation performance and passive avoidance memory, and a decline in hippocampal BDNF, but not PFC. Forced exercise at a moderate intensity alleviated anxiety, cognitive and BDNF defects in morphine-abstinent animals. The high load exercise enhanced serum levels of corticosterone in both saline and morphine groups. Thus, regular moderate forced exercise may be beneficial in preserving cognitive and mood functions in male addicts during the abstinent period and drug rehabilitation.