1H-Nuclear magnetic resonance-based metabolomic analysis of brain in mice with nicotine treatment

Abstract

BackgroundNicotine is rapidly absorbed from cigarette smoke and therefore induces a number of chronic illnesses with the widespread use of tobacco products. Studies have shown a few cerebral metabolites modified by nicotine; however, endogenous metabolic profiling in brain has not been well explored.ResultsH NMR-based on metabonomics was applied to investigate the endogenous metabolic profiling of brain hippocampus, nucleus acumens (NAc), prefrontal cortex (PFC) and striatum. We found that nicotine significantly increased CPP in mice, and some specific cerebral metabolites differentially changed in nicotine-treated mice. These modified metabolites included glutamate, acetylcholine, tryptamine, glucose, lactate, creatine, 3-hydroxybutyrate and nicotinamide-adenine dinucleotide (NAD), which was closely associated with neurotransmitter and energy source. Additionally, glutathione and taurine in hippocampus and striatum, phosphocholine in PFC and glycerol in NAc were significantly modified by nicotine, implying the dysregulation of anti-oxidative stress response and membrane metabolism.ConclusionsNicotine induces significant metabonomic alterations in brain, which are involved in neurotransmitter disturbance, energy metabolism dysregulation, anti-oxidation and membrane function disruptions, as well as amino acid metabolism imbalance. These findings provide a new insight into rewarding effects of nicotine and the underlying mechanism.

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

“…Meanwhile, lactate is metabolized through the TCA, and when compared to glucose, it is equivalent with regard to its access to the TCA in neurons [ 23 ]. After a nicotine CPP paradigm, an increase in lactate was found in the NAc [ 9 ], while nicotine decreased the level of lactate in the NAc and striatum in another study [ 23 ]. The reduced levels of lactate in the urine increased after heroin withdrawal [ 21 ].…”

“…Ketone bodies (3-hydroxybutyrate (3-HB), acetoacetate and acetone) serve as an energy source alternative to glucose for the brain [ 25 ]. A change in 3-HB had also been reported to be induced by nicotine and MA administration [ 9 , 24 ]. In our study, 3-HB and acetoacetate were upregulated in the serum.…”

“…Recently, many studies have applied the metabolomics platform to find molecular markers for drug dependence and some results have been obtained [ 9 – 11 ]. However, none of these studies utilized the SA model, whereas the CPP model has been widely used.…”

Blockade of nicotine sensitization by methanol extracts of Glycyrrhizae radix mediated via antagonism of accumbal oxidative stress

“…RNT increases the production of lipid hydroperoxides in the cerebral cortex and hippocampus of rats [ 31 ]. RNT-induced behavioral sensitization and conditioned place preference in mice occur in conjunction with the dysregulation of accumbal membrane metabolism and an increase in hippocampal MDA production [ 32 , 33 ]. Our group has previously reported that rats self-administering cocaine and methamphetamine show an enhanced production of accumbal ROS, which is associated with sensitized accumbal DA release [ 9 , 10 ].…”

Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

“…To enable a deeper understanding of the underlying mechanisms of the effects of nicotine, endogenous brain metabolites have been investigated in nicotine-addicted mice. Alterations related to neurotransmitter, AA and energy metabolism as well as to the anti-oxidative stress response and membrane metabolism became evident [65].…”