Brain-derived neurotrophic factor levels in morphine-addicted rodents under different exercise protocols: a systematic review and meta-analysis

Exercise might restore morphine-induced behavioural and molecular changes, but related evidence is inconsistent. We conducted a systematic review and meta-analysis of animal studies to elucidate the contribution of brain-derived neurotrophic factor (BDNF) to exercise effects on morphine addiction. We searched papers published until May 25, 2024, in databases, manually searched related references, screened eligible studies, and extracted relevant data. The risk of bias was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE)’s risk bias tool. Subsequently, we summarised study characteristics, reported risks of bias, and conducted a meta-analysis. Subgroup and sensitivity analyses were also conducted. The meta-analysis showed that exercise increased BDNF levels in morphine-addicted male animals, regardless of the exercise type and intensity. Under morphine addiction, voluntary exercise (running wheel) affected BDNF levels in males, whilst forced exercise (treadmill exercise) did not. Furthermore, different exercise intensities did not affect BDNF levels in males. The sensitivity analysis determined that the results were robust. Exercise increased BDNF levels in male but not in female animals. BDNF level changes might be related to the type of exercise but not its intensity. Therefore, BDNF might serve as a biomarker for the effects of different exercise types.