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Impact of Exercise on Tramadol-Conditioned Place Preference
Haneen Amawi1, Alaa M Hammad2, Aseel Abdullah Ibrahim3
1Department of Clinical Pharmacy and Pharmacy Practice, College of Pharmacy, Yarmouk University, Irbid 21163, Jordan.
Brain Sciences
|January 24, 2025
Summary
Forced exercise for 2-4 weeks can reduce tramadol (TRA) seeking behavior by influencing brain-derived neurotrophic factor (BDNF) and interleukin-1 beta (IL-1β) gene expression.
Area of Science:
- Neuroscience
- Pharmacology
- Exercise Physiology
Background:
- Tramadol (TRA) is an opioid analgesic for moderate to severe pain.
- Long-term tramadol use can lead to opioid use disorder (OUD).
Purpose of the Study:
- Investigate the efficacy of forced exercise in mitigating tramadol-seeking behavior.
- Examine the molecular mechanisms underlying exercise's effect on tramadol dependence.
Main Methods:
- Adult male rats underwent tramadol conditioning or were exposed to forced treadmill exercise (2, 4, or 6 weeks) prior to conditioning.
- Tramadol-conditioned place preference (CPP) assessed drug-seeking behavior.
- mRNA expression of BDNF and IL-1β was quantified in the hippocampus, prefrontal cortex, and nucleus accumbens.
Main Results:
- Forced exercise for 2 and 4 weeks significantly attenuated tramadol-seeking behavior.
- This attenuation correlated with increased BDNF mRNA in the hippocampus and nucleus accumbens.
- Exercise reversed tramadol-induced IL-1β elevations in the hippocampus and, for 2-4 weeks, in the prefrontal cortex and nucleus accumbens.
Conclusions:
- Short-term forced exercise (2-4 weeks) effectively reduces tramadol-seeking behavior.
- The observed behavioral changes are associated with the regulation of BDNF and IL-1β gene expression in key brain regions.

