Assessing drug cue-induced brain response in heroin dependents treated by methadone maintenance and protracted abstinence measures
- 10 Downloads
Methadone maintenance treatment (MMT) and protracted abstinence (PA) are common methods of therapy in heroin addiction as both suppress the craving for drug use. However, the difference in patterns of brain function between two groups is unknown. Functional magnetic resonance imaging (fMRI) based drug cue-reactivity task is a good tool to understand the change of brain function during a certain period of treatment. Twenty-three heroin-dependent patients during PA, 18 heroin-dependent patients during MMT and 20 healthy control (HC) individuals were included to conduct the heroin cue-reactivity task during fMRI. The MMT and PA patients’ subjective craving for heroin was evaluated. Differences among the three groups were analyzed with respect to heroin cue induced brain responses. Compared with HC group, MMT and PA groups commonly demonstrated significantly higher brain responses during exposure of heroin-related cues in the bilateral caudate, right thalamus, left hippocampus, parahippocampus, midbrain, left superior parietal lobule, right middle occipital gyrus, left posterior cingulate cortex and right cerebellum. However, compared with PA group, MMT group demonstrated significantly greater brain response mainly in right caudate, hippocampus, midbrain left fusiform, right inferior parietal lobule, left posterior cingulate cortex, cerebellum and postcentral gyrus. No difference in cue induced craving between MMT and PA groups was found. The findings suggest that MMT group demonstrated more enhanced drug cue induced brain responses than PA group, indicating that, these two treatments have different effect on patterns of brain response to heroin related cues in heroin-dependent individuals.
KeywordsHeroin dependence Protracted abstinence Methadone maintenance treatment Craving Functional magnetic resonance imaging
We thank Mr. Xinhai Wu for contributions to the recruitment of heroin-dependent subjects.
This study was funded by National Natural Science Foundation of China (81671661 and 81771813), Technology Innovation Development Foundation of Tangdu Hospital (2013LCYJ003), Reserve Talents Foundation of Tangdu Hospital (2016) and Science and Technology Development Fund of the fourth military medical university (2017XD062). The funding sponsors had no role in the design and conduct of the study; data collection, analysis, and interpretation of the data; preparation, and approval of the manuscript; and decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
All of the authors state that they have no conflicts of interest to declare.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- Bokde, A. L., Lopez-Bayo, P., Meindl, T., Pechler, S., Born, C., Faltraco, F., et al. (2006). Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment. Brain, 129(Pt 5), 1113–1124. https://doi.org/10.1093/brain/awl051.CrossRefGoogle Scholar
- Buckner, R. L., Raichle, M. E., Miezin, F. M., & Petersen, S. E. (1996). Functional anatomic studies of memory retrieval for auditory words and visual pictures. [Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.]. The Journal of Neuroscience, 16(19), 6219–6235.CrossRefGoogle Scholar
- Carbo-Gas, M., Vazquez-Sanroman, D., Aguirre-Manzo, L., Coria-Avila, G. A., Manzo, J., Sanchis-Segura, C., & Miquel, M. (2014). Involving the cerebellum in cocaine-induced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine. Addiction Biology, 19(1), 61–76. https://doi.org/10.1111/adb.12042.CrossRefGoogle Scholar
- Fernando, A., & Wagner, J. C. A. (2002). Into the world of illegal drug use: exposure opportunity and other mechanisms linking the use of alcohol, tobacco, marijuana, and cocaine. American Journal of Epidemiology, 166, 918–925.Google Scholar
- Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100(1), 253–258. https://doi.org/10.1073/pnas.0135058100.CrossRefGoogle Scholar
- Li, Q., Wang, Y., Zhang, Y., Li, W., Yang, W., Zhu, J., Wu, N., Chang, H., Zheng, Y., Qin, W., Zhao, L., Yuan, K., Liu, J., Wang, W., & Tian, J. (2012). Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: an event-related fMRI study. Brain Research, 1469, 63–72. https://doi.org/10.1016/j.brainres.2012.06.024.CrossRefGoogle Scholar
- Li, Q., Wang, Y., Zhang, Y., Li, W., Zhu, J., Zheng, Y., Chen, J., Zhao, L., Zhou, Z., Liu, Y., Wang, W., & Tian, J. (2013). Assessing cue-induced brain response as a function of abstinence duration in heroin-dependent individuals: an event-related fMRI study. PLoS One, 8(5), e62911. https://doi.org/10.1371/journal.pone.0062911.CrossRefGoogle Scholar
- Li, Q., Li, W., Wang, H., Wang, Y., Zhang, Y., Zhu, J., Zheng, Y., Zhang, D., Wang, L., Li, Y., Yan, X., Chang, H., Fan, M., Li, Z., Tian, J., Gold, M. S., Wang, W., & Liu, Y. (2015). Predicting subsequent relapse by drug-related cue-induced brain activation in heroin addiction: an event-related functional magnetic resonance imaging study. Addiction Biology, 20(5), 968–978. https://doi.org/10.1111/adb.12182.CrossRefGoogle Scholar
- Li, W., Li, Q., Wang, Y., Zhu, J., Ye, J., Yan, X., Li, Y., Chen, J., Liu, J., Li, Z., Wang, W., & Liu, Y. (2016). Methadone-induced damage to white matter integrity in methadone maintenance patients: a longitudinal self-control DTI study. Scientific Reports, 6, 19662. https://doi.org/10.1038/srep19662.CrossRefGoogle Scholar
- Rudrauf, D., Lachaux, J. P., Damasio, A., Baillet, S., Hugueville, L., Martinerie, J., Damasio, H., & Renault, B. (2009). Enter feelings: somatosensory responses following early stages of visual induction of emotion. International Journal of Psychophysiology, 72(1), 13–23. https://doi.org/10.1016/j.ijpsycho.2008.03.015.CrossRefGoogle Scholar
- Tabatabaei-Jafari, H., Ekhtiari, H., Ganjgahi, H., Hassani-Abharian, P., Oghabian, M. A., Moradi, A., Sadighi, N., & Zarei, M. (2014). Patterns of brain activation during craving in heroin dependents successfully treated by methadone maintenance and abstinence-based treatments. Journal of Addiction Medicine, 8(2), 123–129. https://doi.org/10.1097/ADM.0000000000000022.CrossRefGoogle Scholar
- Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Childress, A. R., Jayne, M., Ma, Y., & Wong, C. (2006). Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. The Journal of Neuroscience, 26(24), 6583–6588. https://doi.org/10.1523/JNEUROSCI.1544-06.2006.CrossRefGoogle Scholar
- Walter, M., Denier, N., Gerber, H., Schmid, O., Lanz, C., Brenneisen, R., Riecher-Rössler, A., Wiesbeck, G. A., Scheffler, K., Seifritz, E., McGuire, P., Fusar-Poli, P., & Borgwardt, S. (2015). Orbitofrontal response to drug-related stimuli after heroin administration. Addiction Biology, 20(3), 570–579. https://doi.org/10.1111/adb.12145.CrossRefGoogle Scholar
- Wang, Y., Li, W., Li, Q., Yang, W., Zhu, J., & Wang, W. (2011a). White matter impairment in heroin addicts undergoing methadone maintenance treatment and prolonged abstinence: a preliminary DTI study. [research support, non-U.S. Gov't]. Neuroscience Letters, 494(1), 49–53. https://doi.org/10.1016/j.neulet.2011.02.053. CrossRefGoogle Scholar
- Wang, W., Li, Q., Wang, Y., Tian, J., Yang, W., Li, W., Qin, W., Yuan, K., & Liu, J. (2011b). Brain fMRI and craving response to heroin-related cues in patients on methadone maintenance treatment. The American Journal of Drug and Alcohol Abuse, 37(2), 123–130. https://doi.org/10.3109/00952990.2010.543997.CrossRefGoogle Scholar
- Wang, Y., Wang, H., Li, W., Zhu, J., Gold, M. S., Zhang, D., Wang, L., Li, Y., Yan, X., Cheng, J., Li, Q., & Wang, W. (2014). Reduced responses to heroin-cue-induced craving in the dorsal striatum: effects of long-term methadone maintenance treatment. Neuroscience Letters, 581, 120–124. https://doi.org/10.1016/j.neulet.2014.08.026.CrossRefGoogle Scholar
- Xiao, Z., Lee, T., Zhang, J. X., Wu, Q., Wu, R., Weng, X., & Hu, X. (2006). Thirsty heroin addicts show different fMRI activations when exposed to water-related and drug-related cues. Drug and Alcohol Dependence, 83(2), 157–162. https://doi.org/10.1016/j.drugalcdep.2005.11.012.CrossRefGoogle Scholar
- Yacubian, J., Sommer, T., Schroeder, K., Glascher, J., Kalisch, R., Leuenberger, B., Braus, D. F., & Buchel, C. (2007). Gene-gene interaction associated with neural reward sensitivity. Proceedings of the National Academy of Sciences of the United States of America, 104(19), 8125–8130. https://doi.org/10.1073/pnas.0702029104. CrossRefGoogle Scholar
- Zijlstra, F., Veltman, D. J., Booij, J., van den Brink, W., & Franken, I. H. (2009). Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug and Alcohol Dependence, 99(1–3), 183–192. https://doi.org/10.1016/j.drugalcdep.2008.07.012.CrossRefGoogle Scholar