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Updated: Dec 7, 2025

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Sensitivity to Morphine Reward Associates With Gut Dysbiosis in Rats With Morphine-Induced Conditioned Place
Jingyuan Zhang1,2,3,4,5, Jun Yang1,2,3,4,5, Cheng Yang1,2,3,4,5
1Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Gut microbiota has been found to establish a bidirectional relationship with the central nervous system. Variations of the gut microbiota has been implicated in various mental disorders, including opioid use disorders. Morphine exposure has been repeatedly found to disrupt the gut microbiota, but association between the gut microbiota and the sensitivity to morphine reward remains unknown. In this study the conditioned place preference (CPP) paradigm was used for morphine-treated rats and saline-treated rats. After the CPP procedure, the morphine-treated rats were divided equally into the low and high CPP (L- and H-CPP) groups according to the CPP scores. We adopted 16S rRNA sequencing for the fecal bacterial communities at baseline and post-conditioning. By comparing the morphine-treated group with saline-treated group, we found alterations of microbial composition in the morphine-treated group, but no significant differences in alpha diversity. The L-CPP group and H-CPP group differed in microbial composition both before and after morphine treatment. The relative abundance of certain taxa was correlated to the CPP scores, such as Alloprevotella and Romboutsia. This study provides direct evidence that morphine exposure alters the composition of the gut microbiota in rats and that microbial alterations are correlated to the sensitivity to morphine reward. These findings may help develop novel therapeutic and preventive strategies for opioid use disorder.
Insights
Gut microbiota composition changes with morphine exposure and is linked to reward sensitivity. These findings offer potential new strategies for treating opioid use disorder.
Area of Science:
- Microbiology
- Neuroscience
- Pharmacology
Background:
- The gut microbiota and central nervous system share a bidirectional relationship.
- Gut microbiota alterations are linked to mental health disorders, including opioid use disorders.
- Morphine exposure disrupts gut microbiota, but its connection to morphine reward sensitivity is unclear.
Purpose of the Study:
- To investigate the association between gut microbiota composition and morphine reward sensitivity.
- To determine if morphine exposure alters gut microbiota and if these changes correlate with reward sensitivity.
Main Methods:
- Used the conditioned place preference (CPP) paradigm in morphine-treated and saline-treated rats.
- Analyzed fecal bacterial communities using 16S rRNA sequencing at baseline and post-conditioning.
- Compared microbial composition between morphine-treated and saline-treated groups, and between low and high CPP groups.
Main Results:
- Morphine treatment altered gut microbial composition but not alpha diversity compared to saline controls.
- Significant differences in microbial composition existed between low and high CPP groups both before and after morphine treatment.
- Specific taxa, including *Alloprevotella* and *Romboutsia*, showed correlations with CPP scores.
Conclusions:
- Morphine exposure alters gut microbiota composition in rats.
- Gut microbial alterations are correlated with an individual's sensitivity to morphine reward.
- Findings suggest potential for novel therapeutic and preventive strategies for opioid use disorder targeting the gut microbiota.
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