Non-targeted and Targeted Metabolomics Techniques Reveal Striatal Metabolome Characteristics in the Ketamine-Induced Conditioned Place Preference Mice Model.
Weihao Fan, Yi Ye, Hongkun Yang, Ying Wei, Kaiting Shi, Xinyu Yang, Jian Li, Zilong Wang, Yiming Sun, Linchuan Liao
Journal of molecular neuroscience : MN July 12, 2025 DOI: 10.1007/s12031-025-02382-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Topics | Addiction Ketamine Esketamine |
| Keywords | Ketamine addiction ketamine Rewire the brain Neurotransmitters neurotransmitters Kynurenine Dopamine Striatum Reward center Brain's response Metabolomics metabolomics Metabolic pathways Advanced metabolomics Cpp model cpp Cpp mouse model |
| Citations | 1 |
| Key findings | Ketamine-induced conditioned place preference in mice is associated with increased kynurenine and decreased dopamine in the striatum, along with altered metabolic pathways. |
Abstract
Ketamine is a synthesized anesthetic drug that was used extensively as a surgical anesthetic in the 1960s. Currently, ketamine is being investigated extensively for its potential as a treatment for depression. However, the addictive nature of ketamine has become an issue that cannot be ignored at this stage. As of now, there is no clear understanding of the changes in striatal metabolites and their relative metabolic pathways under the addictive effect of ketamine. In this study, a stable model of ketamine-induced conditioned place preference (CPP) was established. Non-targeted metabolomics and targeted metabolomics techniques, based on the ultra-performance liquid chromatography-Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-QE/MS) and the UHPLC-MS platform, were employed to uncover the metabolic characteristics and neurotransmitter profiles of the striatum after ketamine abuse in mice. Potential biomarkers and related differential metabolic pathways of this model have been revealed. In non-targeted metabolomics analysis, striatal differential metabolites mainly involve pathways related to arginine synthesis, purine metabolism, and morphine addiction. In targeted metabolism, the striatum of mice receiving ketamine showed an increase in the content of the neurotransmitter kynurenine (Kyn) and a decrease in the content of the neurotransmitter dopamine (DA). Our study suggested that Kyn and DA metabolism disturbances might be associated with ketamine-induced CPP phenotypes and provided a new perspective for investigating the addiction mechanisms of ketamine.
Comparable studies
Other preclinical and animal studies on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder. Morphine-dependent rats and mice | 2020 | Preclinical study | |
| The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Male and female oxycodone-dependent mice | 2023 | Preclinical study | |
| Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Adolescent rats of both sexes, including naïve and early-life stressed (maternal... | 2025 | Preclinical study | |
| Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. Long Evans rats | 2024 | Preclinical experimental study | |
| Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way. Male and female mice with forebrain ASM overexpression | 2025 | Experimental study |