Research has shown that a large percentage of people in rehabilitation after drug use relapse within the first year. 365 days of resisting temptation seems to end in failure for most, but what if relapse isn’t just a matter of self-control? Addiction research, such as the study done by Dr. Steidl, explores the role of dopamine in the unfortunate sensitization of several drugs and eventual relapse. In 2022, similar research was also done by the Institute of Chinese Medical Sciences at the University of Macau. This study examined how a zebrafish’s single exposure to another drug, morphine, can have long-term impacts on behavior and neurochemistry. Both studies contributed to a better understanding of addiction in many species.
In Dr. Steidl’s study of changes in the sensitization of dopamine, the sample of rodents was split into two groups. One group received drug injections of cocaine in an intermittent pattern, and the other received saline solution as a control. A year later, a delayed challenge test was used to assess re-exposure to cocaine. This test observed behaviors often dependent on dopamine, such as the extent of exploration and locomotor activity. Dr. Steidl concluded that changes in the VTA pathway and glutamate signaling were essential for sensitization in these animals. The cocaine-induced rodents displayed increased reward-seeking traits (e.g., lever pressing), showing a willingness to access more stimulants. This supported the researchers’ hypothesis of addiction and the likelihood of relapse when sensitized.
The research done in Macau by Bian et al. was similar, focusing on the effects of morphine exposure in the sensitization of Danio rerio (adult zebrafish). This species shares many genetic similarities with humans, as they also carry 80% of genes associated with human diseases in their DNA. While their nervous system is much simpler, many of the same pathways are involved in sensitization and could also be used to infer drug impact in humans. The Chinese scientists exposed the species to a single dose of morphine and measured locomotor activity to compare behavioral changes (e.g., drug-seeking) over time. The study observed both acute and chronic behavior in their swimming speed and distance, especially after re-exposure to the drug. After initial exposure, a lower dose (1 mg/L) led to heightened movement, but only with a withdrawal period shorter than 5 to longer than 7 days. Bian et al. concluded that the glutamatergic system is essential in maintaining the dopaminergic effects of morphine. The balance between its transmission and dopamine impacts the extent of such sensitization in mammalian models. Macau scientists also observed that this developed behavior persisted after cessation, demonstrating its endurance. By using zebrafish as a model, the research provides insight into the stages of addiction to many substances, contributing to an understanding of associated neurochemical factors. The simplicity of the species also allows scientists to expand into pharmacological solutions that could alter sensitization and provide therapeutic strategies.
Both studies highlight the vital role of dopamine in addiction and the relapse that follows. While Steidl’s research is focused on the long-term impacts over extended spans, Bian and other scientists were interested in morphine and the effect of a single exposure on vulnerability to relapse. Steidl primarily investigated the mesolimbic network while Bian et al. observed sensitization within the dopamine and glutamate systems. Finally, Bian et al. provide a new perspective to the study of early-stage addiction by foregoing traditional mammalian models for the zebrafish species.
Together, these studies highlight different facets of addiction, from the early sensitization seen in the zebrafish to the complex neurobiological changes found in rodents after extended exposure. Both approaches contribute to the broader understanding of relapse, with the potential to direct future interventions targeting both early and chronic stages of addiction.
Rushika Patel
References
Bian, Y., Wang, X., Liang, J.-H., Li, L., Wu, X., Tang, B., Leung, G. P.-H., & Lee, S. M.-Y. (2025). The development of behavioral sensitization induced by a single morphine exposure in adult zebrafish (Danio rerio). Journal of Neuroscience Research, 45(2), 234–245. https://doi.org/10.1016/j.jnsr.2025.01.014
Puranik, A., Buie, N., Arizanovska, D., Vezina, P., & Steidl, S. (2025). Glutamate inputs from the laterodorsal tegmental nucleus to the ventral tegmental area are essential for the induction of cocaine sensitization in male mice. Neuropharmacology, 67(3), 321–332. https://doi.org/10.1016/j.neuropharm.2025.03.015
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