The Impact of Aerobic Exercise and Psilocybin on Methamphetamine-Induced Histopathological Changes in Rat Cerebral Cortex

Methamphetamine addiction is one of the most prevalent substance use disorders. Augmenting traditional drug treatments with non-pharmacological interventions can enhance treatment efficacy and sustainability. This study aims to investigate the impact of aerobic exercise and psilocybin on histopathological changes in the cerebral cortex of methamphetamine-induced rats.

This experimental research involved 30 female rats randomly allocated into five groups: control, methamphetamine, methamphetamine + aerobic exercise, methamphetamine + psilocybin, and methamphetamine + psilocybin + aerobic exercise. Rats received 15 mg of methamphetamine intraperitoneally every 12 hours for four days. Aerobic exercise was conducted on a treadmill with an 8-week program of escalating intensity, reaching a maximum running time of 30 minutes and speed of 25 m/min, with a 5% slope introduced in the fourth week. Psilocybin was administered intraperitoneally at a microdose of 0.025 mg/kg over 24 sessions. Histopathological changes were assessed using hematoxylin and eosin staining, and descriptive analysis with images was employed to interpret cortical brain tissue samples.

Histological examination revealed tissue and cellular disorganization, altered morphology of pyramidal neurons, and reduced microglial cell counts in methamphetamine-induced rats compared to controls. Endurance training, psilocybin supplementation, and their combination exhibited improvements in tissue and cellular alterations in the cerebral cortex of addicted rats.

 This study demonstrates that exercise training and psilocybin administration in methamphetamine-exposed rats ameliorate cortical histopathology, with the combined intervention yielding the most significant effects. This synergistic effect may reduce the risk of relapse in methamphetamine users by positively modulating brain and central nervous system functions.