Misuse and abuse of drugs are on the increase amongst juvenile individuals across the world. This study was carried out to evaluate the cognitive and subcellular neuropathologic events in the medial prefrontal cortex (mPFC) of juvenile male rats following exposure to alcohol and tramadol hydrochloride. Methods: The rats were assigned into four groups; vehicle group, alcohol group, tramadol group, and the alcohol+tramadol combined group. Twenty-four hours after the administration of the last dose, 5 rats from each group were sacrificed. The mPFCs were excised and were stained with either cresyl violet or glia fibrillary acidic protein immunoreactivity. The remaining rats in each of the groups were subjected to cognitive behavioural tests. Results: The administration of alcohol, tramadol and the co-administration of alcohol+tramadol triggers astrogliosis, glial scars and inflammatory responses relative to the vehicle-treated with well-preserved profile. The distribution of Nissl substances suggested that the neurons are either undergoing neurodegeneration or neuronal metabolism impairment. The behavioural tests showed that the administration of the respective substances impaired cognition in the treated rats compared to the vehicle-treated rats. Conclusion: This study concluded that alcohol, tramadol, and alcohol+tramadol misuse can impair the functional integrity of the medial prefrontal cortex.
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