Introduction: Methamphetamine (METH) misuse induces robust neuroinflammation. Exercise and dietary bioactive may ameliorate this response during withdrawal. We investigated whether aerobic training, a Nutrition BioShield Superfood based on wheat (NBS), or their combination attenuate brain pro-inflammatory cytokine expression in METH-exposed male rats.
Methods: Thirty-six 6-week-old male Wistar rats (180–200 g) were randomized (n=6/group) to: Control (CO), METH (MA), Withdrawal (W), Withdrawal+Training (W/TR), Withdrawal+Supplement (W/SUP), or Withdrawal+Training+Supplement (W/TR+SUP). Animals received intraperitoneal METH twice daily for 6 weeks (week 1: 10 mg/kg; +1 mg/kg weekly; week 6: 15 mg/kg) in 0.9% saline, then underwent 21 days withdrawal as applicable. Aerobic training was performed 6 weeks, 5 days/week at 60% of maximal running speed (re-assessed mid-protocol), 60 min/day after treadmill acclimation. NBS was administered by gavage for 45 days (reported dose 25 g/kg). Twenty-four hours after the final session, brains were collected and IL-1β, TNF-α, and IL-6 mRNA quantified by qRT-PCR; one-way ANOVA with LSD post hoc tested group effects (α=0.05).
Results: Significant group effects were observed for IL-1β (F=298.36, p=0.01), TNF-α (F=602.05, p=0.01), and IL-6 (F=429.96, p=0.01). MA showed higher cytokine expression versus CO, confirming METH-induced neuroinflammation. Relative to W, each intervention (W/TR, W/SUP, W/TR+SUP) reduced IL-1β, TNF-α, and IL-6 expression (p<0.05). Among interventions, W/TR+SUP achieved the lowest cytokine levels overall; for IL-6 it was significantly lower than W/TR (p≈0.04–0.05), indicating an additive benefit of combining training with NBS, whereas W/TR and W/SUP did not differ. For IL-1β and TNF-α, training, NBS, and their combination were comparably effective (not pairwise differences).
Conclusion: In METH-exposed male rats, aerobic training and NBS during withdrawal robustly attenuated brain pro-inflammatory cytokine expression. Combining training with NBS conferred an additional reduction for IL-6. These data support integrating structured aerobic exercise with targeted nutritional support to mitigate METH-related neuroinflammation during recovery.