The Brain's Cannabis System Changes Differently During Morphine Addiction Versus Relapse
The endocannabinoid system in the hippocampus showed opposite patterns during morphine reward expression versus relapse, with enzymes breaking down endocannabinoids increasing during reward and CB1 receptors increasing during relapse.
Quick Facts
What This Study Found
This study examined how endocannabinoid-related genes in the hippocampus change across three phases of morphine addiction: initial reward, extinction, and relapse.
During the expression of morphine reward (conditioned place preference), the hippocampus showed increased expression of FAAH and MAGL, the enzymes that break down the two main endocannabinoids (anandamide and 2-AG). At the same time, CB1 and CB2 receptor expression decreased. This pattern suggests active degradation of endocannabinoid signaling during morphine reward.
During relapse (reinstatement of morphine preference), the pattern reversed: MAGL decreased while CB1 receptor expression increased. This opposite pattern suggests the endocannabinoid system reorganizes between initial drug reward and relapse.
The enzymes that create endocannabinoids (NAPEPLD and DAGL) did not change in any condition, meaning the shifts were driven by changes in degradation and receptor expression rather than production.
Key Numbers
During CPP expression: FAAH and MAGL mRNA increased, CB1R and CB2R decreased. During reinstatement: MAGL decreased, CB1R increased. Biosynthetic enzymes (NAPEPLD, DAGLa/b) unchanged across all conditions.
How They Did This
Mice underwent morphine conditioned place preference (CPP) training, followed by extinction and reinstatement. Quantitative RT-PCR measured expression of endocannabinoid-related genes (CB1R, CB2R, FAAH, MAGL, NAPEPLD, DAGLa/b) in the dorsal hippocampus at each phase.
Why This Research Matters
Understanding how the endocannabinoid system changes during different phases of opioid addiction could lead to phase-specific treatments. The finding that relapse involves different endocannabinoid changes than initial reward suggests that targeting the endocannabinoid system for relapse prevention would require a different approach than targeting initial drug effects.
The Bigger Picture
The opioid crisis has created urgent demand for understanding addiction mechanisms and developing new treatments. This study reveals that the endocannabinoid system, which interacts closely with opioid pathways, undergoes dynamic reorganization across addiction stages, providing potential therapeutic targets.
What This Study Doesn't Tell Us
Gene expression changes do not necessarily translate to protein level or functional changes. The study measured mRNA only, not endocannabinoid levels or receptor activity. Mouse conditioned place preference is a model of drug reward but does not capture all aspects of human addiction.
Questions This Raises
- ?Could FAAH inhibitors prevent morphine reward by maintaining anandamide levels?
- ?Would CB1 receptor antagonists specifically prevent relapse by blocking the increased CB1 signaling?
- ?Do these hippocampal changes parallel changes in other brain regions involved in addiction?
Trust & Context
- Key Stat:
- Endocannabinoid degradation enzymes increased during reward; CB1 receptors increased during relapse
- Evidence Grade:
- Animal study measuring gene expression changes across addiction phases. Preliminary because mRNA changes may not reflect functional outcomes.
- Study Age:
- Published in 2017.
- Original Title:
- Differential expression of endocannabinoid system-related genes in the dorsal hippocampus following expression and reinstatement of morphine conditioned place preference in mice.
- Published In:
- Neuroscience letters, 643, 38-44 (2017)
- Authors:
- Li, Wei(5), Zhang, Cong-Li, Qiu, Zheng-Guo
- Database ID:
- RTHC-01435
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
How does the endocannabinoid system relate to opioid addiction?
This study shows that endocannabinoid genes in the hippocampus change significantly during morphine addiction, with different patterns during initial drug reward versus relapse. This suggests the two systems are deeply interconnected in addiction.
Could targeting the endocannabinoid system help treat opioid addiction?
The finding that different endocannabinoid changes occur during reward versus relapse suggests that yes, but the approach would need to be phase-specific. What helps prevent initial drug reward may differ from what prevents relapse.
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Cite This Study
https://rethinkthc.com/research/RTHC-01435APA
Li, Wei; Zhang, Cong-Li; Qiu, Zheng-Guo. (2017). Differential expression of endocannabinoid system-related genes in the dorsal hippocampus following expression and reinstatement of morphine conditioned place preference in mice.. Neuroscience letters, 643, 38-44. https://doi.org/10.1016/j.neulet.2017.02.025
MLA
Li, Wei, et al. "Differential expression of endocannabinoid system-related genes in the dorsal hippocampus following expression and reinstatement of morphine conditioned place preference in mice.." Neuroscience letters, 2017. https://doi.org/10.1016/j.neulet.2017.02.025
RethinkTHC
RethinkTHC Research Database. "Differential expression of endocannabinoid system-related ge..." RTHC-01435. Retrieved from https://rethinkthc.com/research/li-2017-differential-expression-of-endocannabinoid
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.