Impact of Exercise on Tramadol-Conditioned Place Preference
Background: Tramadol (TRA) is an opioid that is used to manage moderate to severe pain. Long-term use of TRA can lead to the development of opioid use disorder. Objectives: This study investigates the role of forced exercise in reducing TRA-seeking behavior. Methods: Adult male rats (240–260 g) were...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/15/1/89 |
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| Summary: | Background: Tramadol (TRA) is an opioid that is used to manage moderate to severe pain. Long-term use of TRA can lead to the development of opioid use disorder. Objectives: This study investigates the role of forced exercise in reducing TRA-seeking behavior. Methods: Adult male rats (240–260 g) were divided into five groups; the control group received vehicle injections, the TRA group received TRA (75 mg/kg, i.p) every other day for 8 days, and three TRA–exercise groups were forced to run on a treadmill (60 min/day, 5 days/week) for 2, 4, or 6 weeks prior to conditioning with TRA. A tramadol-conditioned place preference (CPP) procedure assessed TRA reinforcement, after which all rats were euthanized, tissue extracted, and mRNA expression for brain-derived neurotrophic factor (<i>Bdnf</i>) and interleukin 1 beta (<i>Il-1β</i>) determined in hippocampus (Hipp), prefrontal cortex (PFC), and nucleus accumbens (NAc). Results: TRA-seeking behavior was seen in the TRA group and the 6 weeks forced exercise group. By contrast, forced exercise for 2 or 4 weeks attenuated TRA-seeking behavior. This attenuation was associated with a significant increase in <i>Bdnf</i> mRNA expression in the Hipp and NAc, but not the PFC. Additionally, the TRA-induced elevations in <i>Il-1β</i> mRNA expression were reversed by all durations of exercise in Hipp. However, only 2 and 4 weeks, but not 6 weeks, of exercise reduced elevations in PFC and NAc <i>Il-1β</i> expression. Conclusion: Forced exercise for 2 and 4 weeks attenuates TRA-seeking behavior partially through the regulation of <i>Bdnf</i> and <i>Il-1β</i> mRNA expression. |
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| ISSN: | 2076-3425 |