scholarly journals Alterations in neurotransmitters targeted metabolomics from the key nuclei of brain reward circuits in cocaine-induced behavioral sensitization for self-administering rats

2021 ◽  
Author(s):  
Yang Li ◽  
Xin Wang ◽  
Shun-nan Ge ◽  
Xue-lian Wang
Keyword(s):  
Metabolic Disease ◽  
Drug Addiction ◽  
Clinical Diagnosis ◽  
Molecular Mechanisms ◽  
Behavioral Sensitization ◽  
Cocaine Addiction ◽  
Targeted Metabolomics ◽  
Measurement Results ◽  
Brain Reward ◽  
Neurotransmitter Metabolites

Abstract Drug addiction can be considered as a metabolic disease because it is triggered by the disruption of metabolism and causes persistent neurochemical disorders that lead to addiction. The purpose of this study was to identify the potential brain biomarkers and the molecular mechanisms in cocaine-induced behavioral sensitization for self-administering rats. UHPLC-MS/MS targeted metabolomics was used to measure 23 neurotransmitters metabolites which may serve as the biological indices underlying the mechanisms of cocaine-induced behavioral sensitization for the key nuclei of brain reward circuits in the process of cocaine addiction. The measurement results showed that there were many changes for many neurotransmitters metabolites in the key nuclei of brain reward circuits (the striatum, the NAc, the hippocampus, the PFC, etc.), but there was no change in the cerebellum during the reconsolidation of drug addiction memory. These findings strongly indicated that many neurotransmitter metabolites in above key nuclei of brain reward circuits participated in cocaine-induced behavioral sensitization for self-administering rats. And it may contribute to a better understanding of metabolic changes in the process of cocaine-induced behavioral sensitization and to be helpful to provide a more integrated view of the molecular underpinnings and to ultimately find biomarkers to assist clinical diagnosis and treatment.

Lithium Pharmacology and a Potential Role of Lithium on Methamphetamine Abuse and Dependence

2019 ◽  
Vol 11 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Nobue Kitanaka ◽  
Frank Scott Hall ◽  
George Richard Uhl ◽  
Junichi Kitanaka
Keyword(s):  
Molecular Mechanisms ◽  
Behavioral Sensitization ◽  
Tryptophan Hydroxylase ◽  
Glycogen Synthase ◽  
Lithium Treatment ◽  
Glycogen Synthase Kinase ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Glycogen Synthase Kinase 3Β ◽  
Methamphetamine Abuse

Background:The effectiveness of lithium salts in neuropsychiatric disorders such as bipolar disorder, Alzheimer’s disease, and treatment-resistant depression has been documented in an extensive scientific literature. Lithium inhibits inositol monophosphatase, inositol polyphosphate 1- phosphatase, and glycogen synthase kinase-3 and decreases expression level of tryptophan hydroxylase 2, conceivably underlying the mood stabilizing effects of lithium, as well as procognitive and neuroprotective effects. However, the exact molecular mechanisms of action of lithium on mood stabilizing and pro-cognitive effects in humans are still largely unknown.Objective:On the basis of the known aspects of lithium pharmacology, this review will discuss the possible mechanisms underlying the therapeutic effects of lithium on positive symptoms of methamphetamine abuse and dependence.Conclusion:It is possible that lithium treatment reduces the amount of newly synthesized phosphatidylinositol, potentially preventing or reversing neuroadaptations contributing to behavioral sensitization induced by methamphetamine. In addition, it is suggested that exposure to repeated doses of methamphetamine induces hyperactivation of glycogen synthase kinase-3β in the nucleus accumbens and in dorsal hippocampus, resulting in a long-term alterations in synaptic plasticity underlying behavioral sensitization as well as other behavioral deficits in memory-related behavior. Therefore it is clear that glycogen synthase kinase-3β inhibitors can be considered as a potential candidate for the treatment of methamphetamine abuse and dependence.

scholarly journals Integrated Transcriptomic and Un-Targeted Metabolomics Analysis Reveals Mulberry Fruit (Morus atropurpurea) in Response to Sclerotiniose Pathogen Ciboria shiraiana Infection

2020 ◽  
Vol 21 (5) ◽  
pp. 1789 ◽  
Author(s):  
Lijun Bao ◽  
Hongpeng Gao ◽  
Zelin Zheng ◽  
Xiaoxiao Zhao ◽  
Minjuan Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Metabolite Profile ◽  
Northwest China ◽  
Targeted Metabolomics ◽  
Mulberry Fruit ◽  
Phenylpropanoid Biosynthesis ◽  
Mapman Analysis ◽  
Mulberry Fruits ◽  
Prevention Methods

Mulberry sclerotiniose caused by Ciboria shiraiana is a devastating disease of mulberry (Morus alba L.) fruit in Northwest China. At present, no disease-resistant varieties are used in production, as the molecular mechanisms of this disease are not well understood. In this study, to explore new prevention methods and provide direction for molecular breeding, transcriptomic sequencing and un-targeted metabolomics were performed on healthy (CK), early-stage diseased (HB1), and middle-stage diseased (HB2) mulberry fruits. Functional annotation, gene ontology, a Kyoto encyclopedia of genes and genomes (KEGG) analysis, and a Mapman analysis of the differentially expressed genes revealed differential regulation of genes related to plant hormone signal transduction, transcription factors, and phenylpropanoid biosynthesis. A correspondence between the transcript pattern and metabolite profile was observed in the phenylpropanoid biosynthesis pathway. It should be noted that the log2 ratio of eugenol (isoeugenol) in HB1 and HB2 are 85 times and 23 times higher than CK, respectively. Our study shows that phenylpropanoid biosynthesis may play an essential role in response to sclerotiniose pathogen infection and eugenol(isoeugenol) enrichment in mulberry fruit, which may provide a novel method for mulberry sclerotiniose control.

scholarly journals Circadian Rhythms, the Mesolimbic Dopaminergic Circuit, and Drug Addiction

2007 ◽  
Vol 7 ◽  
pp. 194-202 ◽  
Author(s):  
Colleen A. McClung
Keyword(s):  
Circadian Rhythms ◽  
Drug Addiction ◽  
Molecular Mechanisms ◽  
Dopaminergic System ◽  
Treatment Options ◽  
Drug Induced ◽  
Circadian Genes ◽  
Dopaminergic Transmission ◽  
Central Pacemaker

Drug addiction is a devastating disease that affects millions of individuals worldwide. Through better understanding of the genetic variations that create a vulnerability for addiction and the molecular mechanisms that underlie the progression of addiction, better treatment options can be created for those that suffer from this condition. Recent studies point to a link between abnormal or disrupted circadian rhythms and the development of addiction. In addition, studies suggest a role for specific genes that make up the molecular clock in the regulation of drug sensitivity, sensitization, and reward. The influence of circadian genes and rhythms on drug-induced behaviors may be mediated through the mesolimbic dopaminergic system. This system has long been implicated in the development of addiction, and recent evidence supports a regulatory role for the brain's central pacemaker and circadian gene expression in the regulation of dopaminergic transmission. This review highlights the association between circadian genes and drug addiction, and the possible role of the mesolimbic dopaminergic system in this association.

Drug addiction: Functional neurotoxicity of the brain reward systems

2001 ◽  
Vol 3 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Friedbert Weiss ◽  
George F. Koob
Keyword(s):  
Drug Addiction ◽  
Reward Systems ◽  
Brain Reward ◽  
The Brain

scholarly journals Influence of Prenatal Methamphetamine Abuse on the Brain

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 14
Author(s):  
Anežka Tomášková ◽  
Romana Šlamberová ◽  
Marie Černá
Keyword(s):  
Czech Republic ◽  
Drug Addiction ◽  
Molecular Mechanisms ◽  
Limited Information ◽  
Sources Of Information ◽  
Variable Response ◽  
Anatomical Structures ◽  
The Czech Republic ◽  
First Choice ◽  
Genetic Mechanisms

Methamphetamine (MA), a psychostimulant, has become a serious problem in recent years. It is one of the most widely abused psychostimulants in the world. In the Czech Republic, ecstasy is the most commonly used non-cannabis drug, followed by hallucinogenic fungi, LSD, MA, cocaine, and finally heroin. The prevalence of the usage of all addictive substances is highest in the age category of 15–34. Approximately 17.2% of registered drug addicts, both male and female, in the Czech Republic use MA as their first-choice drug. This group consists mostly of women who are unemployed and addicted to MA (85%). Almost half of the addicted women switched to MA from other drugs in the course of pregnancy. Psychostimulants such as amphetamine and its synthetic derivate MA induce feelings of calm and happiness by suppressing anxiety and depression. When MA is abused for longer periods, it mimics symptoms of mania and can lead to the development of psychosis. MA is often abused for its anorectic effect, its simple preparation, and compared to heroin and cocaine, its low price. There are significant differences in the susceptibility of users to the stimulant, with reactions to MA fluctuating from person to person. Molecular mechanisms related to the variable response among users might represent an explanation for increased addiction-associated bipolar disorder and psychosis. Currently, there is limited information regarding genetic mechanisms linked to these disorders and the transmission of drug addiction. As such, animal models of drug addiction represent significant sources of information and assets in the research of these issues. The aim of this review is to summarize the mechanism of action of methamphetamine and its effect on pregnant addicted women and their children, including a detailed description of the anatomical structures involved.

Sex differences in lipid metabolism and metabolic disease risk

2012 ◽  
Vol 90 (2) ◽  
pp. 124-141 ◽  
Author(s):  
Michael G. Sugiyama ◽  
Luis B. Agellon
Keyword(s):  
Metabolic Disease ◽  
Sex Differences ◽  
Body Fat ◽  
Molecular Mechanisms ◽  
Sex Chromosome ◽  
Disease Risk ◽  
Treatment Strategies ◽  
Metabolic Complications ◽  
Metabolic Disease Risk ◽  
Organ Systems

The ability of nutrients to regulate specific metabolic pathways is often overshadowed by their role in basic sustenance. Consequently, the mechanisms whereby these nutrients protect against or promote a variety of acquired metabolic syndromes remains poorly understood. Premenopausal women are generally protected from the adverse effects of obesity despite having a greater proportion of body fat than men. Menopause is often associated with a transformation in body fat morphology and a gradual increase in the susceptibility to metabolic complications, eventually reaching the point where women and men are at equal risk. These phenomena are not explained solely by changes in food preference or nutrient intake suggesting an important role for the sex hormones in regulating the metabolic fate of nutrients and protecting against metabolic disease pathophysiology. Here, we discuss how differences in the acquisition, trafficking, and subceullular metabolism of fats and other lipid soluble nutrients in major organ systems can create overt sex-specific phenotypes, modulate metabolic disease risk, and contribute to the rise in obesity in the modern sedentary climate. Identifying the molecular mechanisms underpinning sex differences in fat metabolism requires the unravelling of the interactions among sex chromosome effects, the hormonal milieu, and diet composition. Understanding the mechanisms that give rise to sex differences in metabolism will help to rationalize treatment strategies for the management of sex-specific metabolic disease risk factors.

Cellular and Molecular Mechanisms of Addiction

2017 ◽  
Author(s):  
Kathryn J. Reissner ◽  
Peter W. Kalivas
Keyword(s):  
Molecular Mechanisms ◽  
Drugs Of Abuse ◽  
Drug Seeking ◽  
Molecular Changes ◽  
Cellular Changes ◽  
Continued Use ◽  
Brain Reward ◽  
Social Use ◽  
The Brain

Exposure to drugs of abuse can be a reinforcing experience that, in vulnerable individuals, can lead to continued use and the development of an addiction disorder. Evidence indicates that the escalation in use and compulsive motivation to obtain the drug is linked to long-lasting cellular changes within the brain reward neurocircuitry. In this chapter we describe the stages of transition in use from social use to habitual relapse, and within that context we describe the implicated neurocircuitry, and the enduring cellular and molecular changes that occur within that circuitry, that may mediate the preoccupation with drug seeking in addiction-vulnerable individuals.

New perspectives on cocaine addiction: recent findings from animal research

1989 ◽  
Vol 67 (9) ◽  
pp. 1158-1167 ◽  
Author(s):  
Michael A. Bozarth
Keyword(s):  
Animal Studies ◽  
Physical Dependence ◽  
Reward System ◽  
Cocaine Addiction ◽  
Laboratory Animals ◽  
Self Administration ◽  
Neural Basis ◽  
System Functioning ◽  
Brain Reward ◽  
Brain Reward System

Research with laboratory animals has provided several insights into the nature of cocaine abuse and addiction. First, the nature of drug addiction has been reevaluated and the emphasis has shifted from physical dependence to compulsive drug-taking behavior. Second, animal studies suggest that cocaine is at least as addictive as heroin and possibly even more addictive. Third, cocaine is potentially more dangerous than heroin as evidenced by the higher fatality rate seen in laboratory animals given unlimited access to these drugs. Fourth, the neural basis of cocaine reinforcement has been identified and involves an enhancement of dopaminergic neurotransmission in the ventral tegmental dopamine system. Other addictive drugs (e.g., opiates) may also derive at least part of their reinforcing impact by pharmacologically activating this reward system. Fifth, although the biological consequences of repeated cocaine self-administration on central nervous system functioning are poorly understood, preliminary findings suggest that intravenous cocaine self-administration may decrease neural functioning in this brain reward system. This has important clinical implications because diminished functioning of an important brain reward system may significantly contribute to relapse into cocaine addiction. These and other findings from experimentation with laboratory animals suggest new considerations for the etiology and treatment of drug addiction.Key words: addiction, cocaine, dopamine, reward, withdrawal syndrome.

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