Previous exercise training history reduces drug addiction through brain orexinergic pathway in rodents: Conditioned Place Preference (CPP) model

Methamphetamine, commonly known as METH, is a potent and highly addict-forming stimulant substance that has a significant impact on the brain and poses a substantial health challenge in certain areas. Previous studies have pointed to the involvement of orexinergic pathway in reward-related behavior which is directly involved in acquisition phase of METH induced conditioned place preference (CPP). Besides, while numerous studies have explored the impact of exercise training on METH addiction, there is a limited body of research investigating as a form of preconditioning to prevent drug dependence. In this study, 48 male Wistar rats were assigned into six groups: Saline control, METH1 control, METH2 control, METH1 exercise, METH2 exercise. The exercise groups underwent eight weeks of forced running wheel training, five days a week, at 65% of their maximum running speed (Vmax). Following preconditioning with exercise training, METH groups received intraperitoneal (IP) methamphetamine injections at doses of 1 mg/kg (METH1 control, METH1 exercise) and 2 mg/kg (METH2 control, METH2 exercise) for five days to induce addiction (acquisition phase) according to the CPP model. Immediately following conditioning, hippocampus tissues were extracted to measure OX1R levels using western blotting. The results of the study indicated the conditioning of rats in both METH1 and METH2 control groups while preconditioning with exercise training prevent the addiction with low does of METH and only induced acquisition with double does in METH2 exercise group represented with reduced CPP scores in compare with METH2 control group (p<0.05). Molecular analysis revealed a significant increased in OX1R levels according to METH administration in hippocampus, although exercise training appeared to inhibit OX1R expression. Only conditioning with a high dose of METH was able to increase OX1R levels significantly. As these molecular results are in line with CPP scores it could further support the role of orexinergic pathway in addiction behavior in hippocampus. Furthermore, previous exercise training seems to affect this pathway and prevent conditioning with METH in an effective manner which suggests adaptation in the mesolimbic reward pathway protecting against methamphetamine addiction. Further investigation is warranted to find out the effectiveness of different training interventions in orexinergic pathway to inhibit dependance to METH. In this study, there was no external funding or financial support provided. This work was entirely self-funded by the authors. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.