Pentazocine exposure Elicits Motor-social, Neurochemical, and Neuromorphological Deviations in the Cerebellum of Juvenile Male BALB/c Mice

Abstract

Pentazocine is an opioid used as an analgesic for treating moderate or severe pain. Its abusive use can trigger numerous deleterious effects. We examined the impact of pentazocine administration on the cerebellum of juvenile male mice, focusing on motor-social behaviours, lipid peroxidation, reduced glutathione, superoxide dismutase, catalase, myeloperoxidase, nitric oxide, cyclooxygenase-2, tumour necrosis factor alpha, and sodium-potassium pump (Na+/K+-ATPase), serotonin, dopamine, acetylcholinesterase, and butyrylcholinesterase, as well as mitochondrial functions in the cerebellum of juvenile male mice. The mice were administered 0.25 mL/kg, 0.5 mL/kg, and 0.75 mL/kg of pentazocine dissolved in sterile water for injection s.c. twice daily for 14 days. The results of this study revealed that exposure to pentazocine triggers upregulated activities of increased respective levels of lipid peroxidation, reduced glutathione, superoxide dismutase, catalase, myeloperoxidase, nitric oxide, cyclooxygenase-2, and tumour necrosis factor-alpha, respectively. Our data also showed that exposure to graded doses of pentazocine altered the respective levels of serotonin, dopamine, acetylcholinesterase, and butyrylcholinesterase, with a reduction in the activity of Na+/K+-ATPase. Our experiment further showed that exposure to pentazocine is linked to mitochondrial dysfunctions as well as neuronal degeneration in the cerebellum. Conclusively, our study reveals the significant neurotoxic effects of pentazocine, particularly on motor and social behaviour, along with notable biochemical and neuropathological changes in the cerebellar cortex. These findings suggest that the abusive use of pentazocine causes critical cellular and molecular alterations that contribute to neurotoxicity.