Abstract

Objective: To determine the effect of the most commonly abused drugs (tramadol and morphine), on acetylcholine esterase (AChE), Na+/K+-ATPase activities and related parameters, Na+ and K+ as biomarkers of neurotoxicity. 

Methods: Tramadol - as a weak µ opioid receptor agonist- and morphine - as opiate analgesic drugs, were chosen for the present study. Four series of experimental animals were conducted for either tramadol or morphine: control series; repeated single equal doses (therapeutic dose) series; cumulative increasing doses series and delay (withdrawal) series (96 hours withdrawal period after last administration), at time period intervals 7, 14 and 21 days. Acetylcholine esterase (AChE), Na+/K+-ATPase activities and related parameters, Na+ and K+ were measured in cerebral cortices of experimental rats. 

Results: Acetylcholine esterase (AChE) activity in the brain cerebral cortex increased after the administration of therapeutic repeated doses of either tramadol (20 mg/kg b.w.) or morphine (4 mg/kg b.w.) in different groups. The daily intraperitoneal injection of cumulative increasing dose levels of either tramadol 20, 40 and 80 mg/kg or morphine 4, 8 and 12 mg/kg revealed a significant increase in the mean of acetylcholine esterase activities. The withdrawal groups of either tramadol or morphine showed significant decreases in their levels. Na+/K+ ATPase activity in the brain cerebral cortex of either repeated therapeutic doses of tramadol (20 mg/kg) or morphine repeated therapeutic doses (4 mg/kg) for 21 consecutive days at different intervals 7, 14 and 21 days, induced a significant decrease in the levels of Na+/K+-ATPase in all groups. Withdrawal groups showed a significant decrease in Na+/K+-ATPase level. Furthermore, the daily intraperitoneal injection of cumulative increasing dose levels of either tramadol (20, 40 and 80 mg/kg b.w.) or morphine (4, 8 and12 mg/kg b.w.) induced significant decreases in Na+/K+-ATPase levels in all studied groups. Regarding Na+ and K+, concentrations of either repeated therapeutic doses or cumulative increasing doses at different time intervals, showed different fluctuations in their levels. 

Conclusion: The recorded data suggest that both drugs exert potent effects on AChE and Na+/K+-ATPase activities which could contribute to cerebral cortex malfunction including, memory deficits and the decline in cognitive function observed in chronic users.

 

Keywords: Morphine, Tramadol, Acetylcholine esterase (AChE), Na+/ K+-ATPase
 
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Volume 12, issue 1, January-March 2020


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In April-June 2020 issue, the journal will publish an editorial from Morocco (Dr. Benksim, Higher Institute of Nursing Professions and Health Techniques, Morocco). The editorial talks about lessons from COVID-19 pandemic and the Morocco’s success story. The April-June issue is expected to be published by end of June 2020.


 

The worldwide spread of COVID-19 as an emerging, rapidly evolving situation, and the dramatic need of urgent medicine or vaccine, has rapidly brought new hypotheses for pathophysiology and potential medicinal agents to the fore. It is crucial that the research community provide a way to publish this research in a timely manner.

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The 6th World Conference on Research Integrity (WCRI) is to be held on June 2-5, 2019 in Hong Kong.

The WCRI is the largest and most significant international conference on research integrity. Since the first conference in Lisbon in 2007, it has given researchers, teachers, funding agencies, government officials, journal editors, senior administrators, and research students opportunities to share experiences and to discuss and promote integrity in research. Read more:


 

TDR Clinical Research and Development Fellowships

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Deadline for submission: 7 March 2019, 16:00 (GMT)

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Meta-Analysis Workshops in New York, USA, and London, UK, in April and May 2019

Don't miss this exceptional opportunity to learn how to perform and report a Meta-analysis correctly. Two Meta-analysis workshops are organized in April and May 2019 by Dr. Michael Borenstein in New York, USA (April 08-10, 2019) and London, UK (May 27-29).

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Dr. Michael Borenstein, one of the authors of Introduction to Meta-Analysis, is widely recognized for his ability to make statistical concepts accessible to researchers as well as to statisticians. He has lectured widely on meta-analysis, including at the NIH, CDC, and FDA. Read more: