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Treadmill Exercise Training Ameliorates Apoptotic Cells and DNA Oxidation in the Cerebral Cortex of Rats Exposed to Chronic Ketamine Abuse.

Salar Sabziparvar, Kazem Khodaei, Javad Tolouei Azar

Addiction Biology March 1, 2025 DOI: 10.1111/adb.70025 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 24
Population Wistar rats
Interventions Ketamine Moderate-intensity continuous training (MICT)
Dose 50 mg/kg/day
Duration 8-week ketamine administration, 8-week exercise intervention post-withdrawal
Topics Addiction Ketamine Esketamine
Keywords Brain health Apoptosis Drug abuse Oxidative stress Addiction recovery Exercise therapy Substance abuse treatment
Citations 1
Key findings Moderate-intensity continuous training after chronic ketamine abuse reduces apoptosis and oxidative damage in the rat cerebral cortex.

Abstract

Ketamine abuse damages brain function and structure, increasing reactive oxygen species and apoptosis in the cerebral cortex, but moderate-intensity continuous training (MICT) can enhance antioxidant defences and reduce apoptosis. Therefore, we aimed to answer whether MICT can reduce the side effects of chronic ketamine abuse. 24 Wistar rats were split into control (CON), ketamine abuse (KET), exercise after ketamine withdrawal (KET + EX), and non-intervention ketamine withdrawal (KET + WD) groups. Ketamine intervention groups received 50 mg/kg/day ketamine for 8 weeks; KET + EX underwent 5 MICT sessions/week at 60-75% VO2max for 8 weeks post-withdrawal. Post-sampling of cerebral cortex, we evaluated histological changes, apoptotic cell numbers, Bax, Bcl-2, Caspase-3 mRNA/protein, 8-oxo-2'-deoxyguanosine (OXO) expression, glutathione peroxidase (GPX) and glutathione reductase (GR) mRNA and other oxidative stress and antioxidant markers levels. Effect sizes (ES) were used to assess group differences. MICT significantly reduced apoptotic cells (ES = 14.24, p < 0.0001), decreased Bax and caspase-3 protein expression, and increased Bcl-2 compared to the KET group (Bax: ES = 2.77, p = 0.005; caspase-3: ES = 7.73, p < 0.0001; Bcl-2: ES = 12.11, p < 0.001). It also lowered Bax and caspase-3 mRNA (Bax: ES = 4, p = 0.014; caspase-3: ES = 2.29, p = 0.024). MICT reduced OXO and increased GR and GPX mRNA and nitric oxide (NO) level (GR: ES = 2.02, p = 0.016; GPX: ES = 1.98, p = 0.035; OXO: ES = 11.39, p < 0.0001; NO: ES = 3.52, p = 0.003). Levels of malondialdehyde, myeloperoxidase, glutathione, superoxide dismutase, and catalase remained unchanged between groups. MICT seems effective in reducing apoptosis and oxidative damage in the cerebral cortex of rats with long-term ketamine abuse.

Comparable studies

Other preclinical and animal studies on ketamine for addiction, most cited first.

Study Year Design Participants
R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder. Morphine-dependent rats and mice 2020 Preclinical study
The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Male and female oxycodone-dependent mice 2023 Preclinical study
Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Adolescent rats of both sexes, including naïve and early-life stressed (maternal... 2025 Preclinical study
Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. Long Evans rats 2024 Preclinical experimental study
Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way. Male and female mice with forebrain ASM overexpression 2025 Experimental study

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