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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2025-01-01
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| author | Haneen Amawi Alaa M. Hammad Aseel Abdullah Ibrahim Nosyba Alsbih Frank Scott Hall Fawaz Alasmari Bahaa Al-Trad |
| author_facet | Haneen Amawi Alaa M. Hammad Aseel Abdullah Ibrahim Nosyba Alsbih Frank Scott Hall Fawaz Alasmari Bahaa Al-Trad |
| author_sort | Haneen Amawi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-240424f2b2ae4a4ba9fa4b15afb11923 |
| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj-art-240424f2b2ae4a4ba9fa4b15afb119232025-01-24T13:25:56ZengMDPI AGBrain Sciences2076-34252025-01-011518910.3390/brainsci15010089Impact of Exercise on Tramadol-Conditioned Place PreferenceHaneen Amawi0Alaa M. Hammad1Aseel Abdullah Ibrahim2Nosyba Alsbih3Frank Scott Hall4Fawaz Alasmari5Bahaa Al-Trad6Department of Clinical Pharmacy and Pharmacy Practice, College of Pharmacy, Yarmouk University, Irbid 21163, JordanDepartment of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, JordanDepartment of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 21163, JordanDepartment of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 21163, JordanDepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USADepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 21163, JordanBackground: 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.https://www.mdpi.com/2076-3425/15/1/89<i>Bdnf</i>conditioned place preferenceexercise<i>Il-1β</i>tramadol |
| spellingShingle | Haneen Amawi Alaa M. Hammad Aseel Abdullah Ibrahim Nosyba Alsbih Frank Scott Hall Fawaz Alasmari Bahaa Al-Trad Impact of Exercise on Tramadol-Conditioned Place Preference Brain Sciences <i>Bdnf</i> conditioned place preference exercise <i>Il-1β</i> tramadol |
| title | Impact of Exercise on Tramadol-Conditioned Place Preference |
| title_full | Impact of Exercise on Tramadol-Conditioned Place Preference |
| title_fullStr | Impact of Exercise on Tramadol-Conditioned Place Preference |
| title_full_unstemmed | Impact of Exercise on Tramadol-Conditioned Place Preference |
| title_short | Impact of Exercise on Tramadol-Conditioned Place Preference |
| title_sort | impact of exercise on tramadol conditioned place preference |
| topic | <i>Bdnf</i> conditioned place preference exercise <i>Il-1β</i> tramadol |
| url | https://www.mdpi.com/2076-3425/15/1/89 |
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