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Early-life stress alters sleep structure and the excitatory-inhibitory balance in the nucleus accumbens in aged mice

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Chinese Medical Journal 2019年第13期132卷 1582-1590页

作者： Ting Wang Hong-Li Wang Rui Liu Han Wang Yue Zhang Ya-Xin Sun Yun-Ai Su Tian-Mei Si Ji-Tao Li National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital/lnstitute of Mental Health)and the Key Laboratory of Mental Health Ministry of Health(Peking University)Beijing 100191China

Background:Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations.One deleterious effect of early-life stress that manifests in later life is sleep disturbance,but this has not been examined in aged mice and the underlying neural mechanisms remain unknown.Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation,this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.Methods:Twenty aged male C57BL/6 mice (>16 months,n =10 per group) were used in this study.During post-natal days 2 to 9,dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed).When the mice were 16 to 17 months old,their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram.The amount of each sleep-wake stage,mean duration,and stage transition was analyzed.Then,five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry.Group comparisons were carried out using Student t test or analysis of variances when appropriate.Results:Compared with the control mice,the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs.631.33 ± 34.73 min,t17 =2.376,P =0.030),accordingly,non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs.723.54 ± 39.21 min,t17 =2.326,P =0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs.89.39 ± 12.69 min,t17 =3.277,P =0.004).Meanwhile,we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1,16) =81.04,P < 0.001).Conclusion:Early adverse experiences disrupt sleep behaviors in aged mice,which might be ass

关键词： Early-life stress Sleep Aging Nucleus accumbens Mice

THE INTERACTION BETWEEN PERIAQUEDUCTAL GRAY AND NUCLEUS accumbens IN ACCELER-ATING THE RELEASE OF ENKEPHALINS AND β-ENDORPHIN

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Chinese Science Bulletin 1991年第24期36卷 2083-2087页

作者：马青平石玉顺韩济生 Neuroscience Research Center Beijing Medical UniversityBeijing 100083 PRC

There is a growing body of evidence showing that periaqueductal gray (PAG) and nucleus accumbens (N. accumbens) play important roles in the modulation of nociception. In our previous study of the mechanisms of morphine analgesia we found that opioid antagonist naloxone injected into either of the two nuclei, PAG or N. accumbens, could

关键词： periaqueductal gray (PAG) nucleus accumbens enkephalins and β-endorphin

Role of prefrontal cortex-nucleus accumbens glutamatergic projection in heroin reward and motivation

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中国药理学与毒理学杂志 2018年第9期32卷 725-726页

作者： ZHU Hua-qiang LAI Miao-jun XU Wen-jin ZHUANG Ding-ding FU Dan HONG Qing-xiao LIU Hui-fen ZHOU Wen-hua Laboratory of Behavioral Neuroscience Ningbo Addiction Research and Treatment Center School of Medicine Ningbo University Ningbo 315010 China

OBJECTIVE Glutamatergic projections from prefrontal cortex(PFc) to nucleus accumbens(NAc) regulate the dopamine(DA) release in NAc.However,it is not clear whether this circuit is effective for the reward and motivation of heroin addiction.Our study investigates the effects of metabotropic glutamate receptor 2/3(mGluR2/3) and the projections from ventromedial prefrontal cortex(vmPFc) to the NAc shell on the reward and motivation of heroin-addicted rats.METHODS First,rats were trained to selfadministration for 14 d.On the 15 thday,parts of rats were injected with mGluR 2/3 agonist LY379268(0.1,0.3 and 1.0 mg·kg-1,ip) systematically and another parts of rats were bilaterally microinjected with LY379268(0.3 and 1.0 g·L^(-1))at the volume of 0.5 μL into the ventral tegmental area(VTA),NAc core or NAc shell,respectively.All rats were followed by heroin self-administration testing under fixed ratio 1(FR1) schedule or progressed ratio(PR) schedule to observe the effect of LY379268 on the heroin reward or motivation.Second,rats were injected chemogenetic glutamatergic virus(pAAV-CaMKIIa-hM3 D(Gq)-mCherry or pAOV-CaMKIIa-hM4 D(Gi)-mCherry-3 Flag) or negative control virus in vmPFc,and trained to heroin self-administration for 14 d.On the 15 thday,rats were bilateral y microinjected with clozapine-N-oxide(CNO,1 mmol·L^(-1),0.5 μL) into NAc shell and tested the effect on the heroin reward or motivation.Finally,rats were injected optogenetical glutamatergic virus(AAV2/9-CaM KⅡ-hChR2-EYFP) or negative control virus in vmPFc,implanted 16 channel photoelectrode in ipsilateral NAc shell,and trained to heroin selfadministration for 14 d.On the 15 thday,rats were tested heroin reward under FR1 procedure with blue light stimulation in the wavelength of470 nm,frequency of 25 HZ and power of 5 mW.Each stimulation lasting for 1 h and interval for1 h.The spike changes before and after stimulation in NAc Shel neural nerve was recorded.RESULTS LY379268 cloud dose-dependent attenuated the heroin reward or motivation and the local effective

关键词： heroin ventromedial prefrontal cortex nucleus accumbens metabotropic glutamatereceptor 2/3 reward motivation

Effect of Aqueous Extract of <i>Phoenix dactylifera</i>Pollen on Dopamine System of Nucleus accumbens in Male Rats

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Neuroscience & Medicine 2014年第1期5卷 49-59页

作者： Ali Abedi Seyyed Morteza Karimian Mohsen Parviz Perham Mohammadi Hamid Reza Sadeghipour Roudsari Pharmacology Department School of Pharmacy Ar-dabil University of Medical Sciences Ardabil Iran Physiology Department Faculty of Medicine Ardabil University of Medical Sciences Ardabil Iran Physiology Department Faculty of Medicine Tehran University of Medical Sciences Tehran Iran

Background: Dopamine has been known to facilitate male sexual function. Methods: The effect of aqueous extract (140 mg/kg) of Phoenix dactylifera date palm pollen on sexual behavior and determining of dopamine transmission in the nucleus accumbens was studied in male rats using in vivo microdialysis. Results: Releasing of dopamine increased significantly in the nucleus accumbens when a receptive female was introduced behind a screen (p 0.001). During copulation, dopamine increased markedly in control and treated rats. Phoenix dactylifera Date Palm Pollen enhanced the orientation of males towards females by increasing mounting and ano-genital investigatory behavior. Improving of sexual behavior and dopamine release was higher in treated rats in comparison with control (p 0.001). Conclusion: These results indicate a neurochemical basis for interaction between dopaminergic agents and male sexual behavior. Therefore, Phoenix dactylifera Date Palm Pollen seems to act as a dopamine agonist and to cure male infertility. It can be used as an aphrodisiac that leads to further increases in dopamine release.

关键词： Phoenix dactylifera Date Palm Pollen Dopamine Nucleus accumbens Microdialysis Male Rat

Nucleus accumbens stereotactic surgery: Achieving accuracy through area M

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World Journal of Neurology 2013年第2期3卷 7-9页

作者： Ioannis N Mavridis Medical office of the Command of the Hellenic Navy General Staff (Naval Hospital of Athens) 15561 Athens Greece

The nucleus accumbens(NA), a major pleasure center of the human brain, is a limbic-motor interface involved in several neurological and psychiatric disorders. During the last decade, this nucleus is also a deep brain stimulation target for selected patients. Purpose of this paper is to comment on the article entitled "Stereotactic anatomy of the human nucleus accumbens: from applied mathematics to microsurgical accuracy" which was recently published in "Surgical and Radiologic Anatomy" and is one of the latest articles on NA anatomy and surgery. The described results included a probabilitybased guide for in vivo(side-depended) stereotactic localization of the human NA and a standard for the NA, specific stereotactic zone of the human brain(which can be used in combination for an accurate stereotactic NA targeting). Furthermore, two specific stereotactically standard NA areas were found which could be used as abundant stereotactic guides for targeting of the anterior limb of the internal capsule, with electrode's contact 0(lowest) placed in the vicinity of the NA. However, the most important finding of this paper was standard area M(Mavridis' area), which is the most reliable stereotactically standard area of the human NA, regardless of side or gender, useful for highly accurate stereotacticNA targeting.

关键词： Mavridis'area Deep brain stimulation Neuropsychiatric disorders Nucleus accumbens Stereotactic surgery Surgical accuracy

Differential Effects of Voluntary Ethanol Consumption on Dopamine Output in the Nucleus accumbens Shell of Roman High- and Low-Avoidance Rats: A Behavioral and Brain Microdialysis Study

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World Journal of Neuroscience 2014年第3期4卷 279-292页

作者： Maria G. Corda Giovanna Piras Maria A. Piludu Osvaldo Giorgi Department of Life and Environmental Sciences Section of Pharmacological Pharmaceutical and Nutraceutical Sciences University of Cagliari Cagliari Italy

The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2% - 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to na?ve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats.

关键词： Roman High- and Low-Avoidance Rats Voluntary Ethanol Consumption Mesolimbic Dopaminergic System Nucleus accumbens Shell Novelty-Seeking Behavior

Role of mesocorticolimbic DA system in reinstatement induced by cue

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中国药理学与毒理学杂志 2018年第9期32卷 716-717页

作者： JING Man-yi HAN Xiao ZHAO Tai-yun LIU Wen-feng SONG Rui LI Jin Institute of Pharmacology and Toxicology Academy of Military Medical Sciences Academy of Mililtary Sciences Beijing 100850 China

OBJECTIVE Dopamine(DA)plays important roles in Pavlovian conditioning by mediating reward,learning and motivation.While the conditioning stimulation(CS) is the most important inducement for reinstatement in addiction.The present study investigated the specific role of the DA projections to nucleus accumbens(NAc) and medial prefrontal cortices(mPFC) from ventral tegmental area(VTA) in reinstatement induced by cue.METHODS(1)Optogenetic intracranial self-stimulation and reinstatement.DAT-Cre transgenic mice received an injection of adeno-associated viral vectors encoding channelrhodopsin2(ChR2) or control vector into the VTA resulting in the selective expression of these opsins in DA neurons.Then,we stimulated the VTA,NAc(core and shel) or mP FC [prelimbic cortex(PL) and infralimbic cortex(IL)] via an optical fiber.In the reinforcement test,the mice with ChR2 learned instrumental responses corresponding to the delivery of photostimulation into the VTA with multiple frequencies and during time;in the reinstatement phase,stimulation of the DA projections to NAc(core or shell) or mPFC(IL and PL) from VTA to induce reinstatement after 2 weeks of extinction of self-stimulation.(2)Reinstatement in cocaine self-administration.Virus encoding ChR2 or hM4 Di were injected into VTA of DAT-Cre transgenic mice.The mice with ChR2 and hM4 Di in DA neurons were trained to establish self-administration of cocaine.After 2 weeks of extinction,laser stimulation of the DA projections to NAc(core or shel) or mP FC(IL and PL) was conducted to induce reinstatement.After that,Clozapine was injected in NAc core to test the impacts of VTA-NAc core depression on the reinstatement induced by cue.(3) Photometry of VTA DA neurons in reinstatement.DAT-Cre transgenic mice were received an injection of AAV-DIO-Gcamp6 m into VTA.After cocaine self-administration and extinction,mice with Gcamp6 m were challenged by cue(paired with cocaine previously) and the photometry of VTA DA neurons was conducted during the reinstatement.RESULTS(1)The enhanced sel

关键词： dopamine ventral tegmental area nucleus accumbens core and shell medial prefrontal cortex self-stimulation reinstatement

Further studies on the effects of acamprosate on tolerance to the analgesic effects of morphine and NO synthesis in the brain

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Health 2013年第11期5卷 1-6页

作者： Jacqueline Sepúlveda Andrea Ortega Jorge Roa Enrique Contreras Department of Pharmacology School of Biological Sciences University of Concepción Concepción Chile Department of Pharmacology School of Biological Sciences University of Concepción Concepción Chile Department of Physiology School of Biological Sciences University of Concepción Concepción Chile Department of Pre-Clinical and Clinical Sciences School of Medicine Catholic University of the Holy Conception Concepción Chile

The aim of this work was to investigate whether acamprosate modifies the expression of the enzyme responsible for neuronal NO synthesis (nNOS) in the nucleus accumbens (NAc) of mice chronically treated with morphine and during the abstinence syndrome induced by naloxone. The enzyme was monitored by the NADPH diaphorase method. The number of cells stained for NADPH diaphorase in the NAc of mice was counted in 40 μm thick coronal brain slices at 40X. The intensity of the histochemical reaction of stained cells from naive morphine plus saline and morphine plus acamprosate treated mice was analyzed by Image Pro Plus 4.5.1. Morphine administered in a slow release preparation increased the stain intensity of the positive neurons. The increase in the NADPH staining persisted after naloxone was given to mice chronically treated with morphine. Acamprosate antagonized the effects induced by chronic morphine treatment in the NAc of mice. These results indicate that up-regulation of nNOS in the NAc is a consequence of the sustained effects of morphine stimulation, which, in turn, may result from an increased in glutamate release during the abstinence syndrome.

关键词： Morphine Nitric Oxide Nucleus accumbens Acamprosate

DNA methylation of the Monoamine Oxidases A and B genes in postmortem brains of subjects with schizophrenia

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Open Journal of Psychiatry 2012年第4期2卷 374-383页

作者： Qiaohui Yang Keiko Ikemoto Satoshi Nishino Junko Yamaki Yasuto Kunii Akira Wada Yoshimi Homma Shin-Ichi Niwa Department of Biomolecular Science School of Medicine Fukushima Medical University Fukushima Japan Department of Neuropsychiatry School of Medicine Fukushima Medical University Fukushima Japan

Aims: We focused on DNA methylation of the promoter regions of the Monoamine Oxidase (MAO) A and B genes from postmortem brains of subjects with schizophrenia. Methods: We determined levels of DNA methylation using genomic DNA samples purified from four brain areas: prefrontal cortex (PFC), hippocampus, occipital cortex and nucleus accumbens (NAc), by a bisulfite sequencing method from seven normal subjects and six subjects with schizophrenia. Results: Although very few methylated CpGs of the MAOA and MAOB genes were detected in male samples, various DNA methylation patterns were present in female samples, and some differences were found in such patterns between normal subjects and subjects with schizophrenia. In the PFC, the average level of methylation of both genes was significantly higher in subjects with schizophrenia than in normal subjects. The content of highly methylated alleles of the MAOA gene in the NAc was significantly associated with schizophrenia, with similar results obtained for the MAOB gene in both the NAc and PFC. Some CpG sites showed higher levels of methylation in schizophrenia than in normal subjects. Conclusions: Levels of methylation were quite high in NAc and PFC in female subjects with schizophrenia compared with those in female normal subjects.

关键词： DNA Methylation Monoamine Oxidase Nucleus accumbens Postmortem Brain Schizophrenia