Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1H-nuclear magnetic resonance spectra

Abstract

BackgroundUnderstanding the process of relapse to abused drugs and ultimately developing treatments that can reduce the incidence of relapse remains the primary goal for the study of substance dependence. Therefore, exploring the metabolite characteristics during the relapse stage is valuable.MethodsA heroin self-administered rat model was employed, and analysis of the 1H-nuclear magnetic resonance-based metabolomics was performed to investigate the characteristic metabolite profile upon reintroduction to the drug after abstinence.ResultsSixteen metabolites in the serum of rats, including phospholipids, intermediates in TCA (Tricarboxylic Acid Cycle) cycle, keto bodies, and precursors for neurotransmitters, underwent a significant change in the reinstatement stage compared with those in the control group. In particular, energy production was greatly disturbed as evidenced by different aspects such as an increase in glucose and decrease in intermediates of glycolysis and the TCA cycle. The finding that the level of 3-hydroxybutyrate and acetoacetate increased significantly suggested that energy production was activated from fatty acids. The concentration of phenylalanine, glutamine, and choline, the precursors of major neurotransmitters, increased during the reinstatement stage which indicated that an alteration in neurotransmitters in the brain might occur along with the disturbance in substrate supply in the circulatory system.ConclusionsHeroin reinforcement resulted in impaired energy production via different pathways, including glycolysis, the TCA cycle, keto body metabolism, etc. A disturbance in the substrate supply in the circulatory system may partly explain heroin toxicity in the central nervous system. These findings provide new insight into the mechanism underlying the relapse to heroin use.Electronic supplementary materialThe online version of this article (10.1186/s12868-018-0404-5) contains supplementary material, which is available to authorized users.

Forensic NMR metabolomics: one more arrow in the quiver

“…The effects of another addictive opioid, i.e. heroin (3,6-diacetylmorphine), were investigated using a heroin self-administration rat model (Ning et al 2018 ). The authors focused their attention on the serum metabolic modifications occurring upon reinforcement (heroin reintroduction) after abstinence.…”

Gc-MS Based Metabolic Profile of Brain Tissue in Common Carp Following Acute Exposure to Cypermethrin.

“…In the present study, CYP exposure caused a significant elevation in the level of glutamine (P < 0.05) in L-group at 24 h and in H-group at 24 and 96 h. In addition to, a significant increase in the level of glutamate in H-group at both time points ( Fig.2-A, Table.1). Glutamine is the precursor for glutamate synthesis and plays a vital role in removing excess of nitrogen from brain suggesting that CYP allowed excessive accumulation of nitrogen in the brain of carp (Ning et al 2018). The rise in glutamate (P < 0.05), an excitatory neurotransmitter, in brain tissue was previously reported in the brain of goldfish exposed to lambda-cyhalothrin (Li et al 2014).…”

“…In the current study, higher concentration of CYP (1 μg/L) increased the level of tyrosine (P < 0.05) at 96 h (Fig.2-B). In the liver, tyrosine is synthetized from phenylalanine and then converted into L-3, 4-dihydroxyphenylalanine (L-DOPA) in brain tissue (Ning et al 2018). A previous study in young rat reported that prenatal exposure to fenvalerate resulted in disruption in dopaminergic receptors (Malaviya et al 1993).…”

Metabolomic Strategies in Biomarker Research–New Approach for Indirect Identification of Drug Consumption and Sample Manipulation in Clinical and Forensic Toxicology?

“…However, it was found that no single analytical platform is capable of capturing all metabolomics information in a single run (Dinis-Oliveira, 2014). LC- and GC-MS, nuclear magnetic resonance (NMR) spectroscopy, and LC with electrochemical detection are all used (Ning et al, 2018), but the most widespread analytical instruments utilized are MS and NMR spectroscopy. The advantages and disadvantages of MS or NMR use within the field of metabolomics have been extensively discussed in corresponding reviews (Schlotterbeck et al, 2006; Pan and Raftery, 2007).…”

“…From a pharmacological point of view this is not surprising. As stated e.g., by Ning et al neuronal activity is extremely energy demanding, and the brain energy supply requires oxidative metabolism of glucose in mitochondria and demands lactic acid from glycolytic processes (Ning et al, 2018). However, albeit e.g., MA and GHB act at different pharmacological targets both were shown to influence succinate concentrations (Zheng et al, 2014; Palomino-Schatzlein et al, 2017).…”