Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.

Abstract

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats.

• Authors: Leila Ahmad-Molaei, Mahsa Pourhamzeh, Reza Ahadi, Fariba Khodagholi, Hossein Hassanian-Moghaddam, Abbas Haghparast
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 41 Issue 8 Pg. 1635-1649 (Nov 2021) ISSN: 1573-6830 [Electronic] United States
• PMID: 32712727 (Publication Type: Journal Article)
• Copyright: © 2020. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Analgesics, Opioid
• Biomarkers
• Inflammation Mediators
• S100 Calcium Binding Protein beta Subunit
• S100b protein, rat
• Phosphopyruvate Hydratase
• Methadone

Topics

• Age Factors
• Analgesics, Opioid (toxicity)
• Animals
• Biomarkers (blood)
• Brain (drug effects, metabolism, pathology)
• Drug Overdose (blood, metabolism, pathology)
• Inflammation Mediators (blood)
• Male
• Maze Learning (drug effects, physiology)
• Memory, Short-Term (drug effects, physiology)
• Methadone (toxicity)
• Phosphopyruvate Hydratase (blood)
• Rats
• Rats, Wistar
• S100 Calcium Binding Protein beta Subunit (blood)
• Time Factors