Publications by authors named "Xinhe Liu"

30 Publications

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Formalin-induced pain prolongs sub- to supra-second time estimation in rats.

PeerJ 2021 2;9:e11002. Epub 2021 Mar 2.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Background: Temporal estimation can be influenced by pain, which is a complex psychological and physiological phenomenon. However, the time range in which perception is most sensitive to pain remains unclear.

Methods: In the present study, we explored the effects of acute inflammatory pain on time perception in the sub- to supra-second (0.6-2.4-s) and supra-second (2-8-s) ranges in rats. Plantar formalin injection was used to induce acute inflammatory pain, and a temporal bisection task was used to measure time perception. Task test sessions were held for five consecutive days (one per day): the day before injection (baseline), immediately after injection, and the three post-injection days. The point of subjective equality (PSE, which reflects the subjective duration) and Weber fraction (which reflects temporal sensitivity) were calculated and analysed.

Results: In the 0.6-2.4-s range, the PSE was significantly lower, indicating prolonged subjective duration, in the formalin group relative to the saline group ( = 0.049) immediately after injection. Formalin-induced pain also tended to lengthened time perception in the 0.6-2.4-s range on post-injection days 2 ( = 0.06) and 3 ( = 0.054). In the 2-8-s range, formalin injection did not affect the PSE or Weber fraction.

Conclusions: The enhanced effect of pain on temporal perception in the sub- to supra-second range is observed in this study and this effect is attenuated with the prolongation of estimated time, even in rats.
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http://dx.doi.org/10.7717/peerj.11002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934679PMC
March 2021

Improving the activity and thermostability of GH2 β-glucuronidases via domain reassembly.

Biotechnol Bioeng 2021 May 19;118(5):1962-1972. Epub 2021 Feb 19.

Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Institute of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, PR China.

Glycoside hydrolase family 2 (GH2) enzymes are generally composed of three domains: TIM-barrel domain (TIM), immunoglobulin-like β-sandwich domain (ISD), and sugar-binding domain (SBD). The combination of these three domains yields multiple structural combinations with different properties. Theoretically, the drawbacks of a given GH2 fold may be circumvented by efficiently reassembling the three domains. However, very few successful cases have been reported. In this study, we used six GH2 β-glucuronidases (GUSs) from bacteria, fungi, or humans as model enzymes and constructed a series of mutants by reassembling the domains from different GUSs. The mutants PGUS-At, GUS-PAA, and GUS-PAP, with reassembled domains from fungal GUSs, showed improved expression levels, activity, and thermostability, respectively. Specifically, compared to the parental enzyme, the mutant PGUS-At displayed 3.8 times higher expression, the mutant GUS-PAA displayed 1.0 time higher catalytic efficiency (k /K ), and the mutant GUS-PAP displayed 7.5 times higher thermostability at 65°C. Furthermore, two-hybrid mutants, GUS-AEA and GUS-PEP, were constructed with the ISD from a bacterial GUS and SBD and TIM domain from fungal GUSs. GUS-AEA and GUS-PEP showed 30.4% and 23.0% higher thermostability than GUS-PAP, respectively. Finally, molecular dynamics simulations were conducted to uncover the molecular reasons for the increased thermostability of the mutant.
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http://dx.doi.org/10.1002/bit.27710DOI Listing
May 2021

Dual-path modulation of hydrogen peroxide to ameliorate hypoxia for enhancing photodynamic/starvation synergistic therapy.

J Mater Chem B 2020 11;8(43):9933-9942

Jiangsu Collaborative Innovation Center of Biomedical Functional Materials and Jiangsu Key Laboratory of Biofunctional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙-) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.
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http://dx.doi.org/10.1039/d0tb01556cDOI Listing
November 2020

Molecular dynamics exploring of atmosphere components interacting with lung surfactant phospholipid bilayers.

Sci Total Environ 2020 Nov 26;743:140547. Epub 2020 Jun 26.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

Sulfur dioxide (SO), nitrogen oxide (NO) and ozone (O) in the atmosphere are significantly correlated with various respiratory and cardiovascular diseases. High doses of each of these gases or a mixture can change the physical and chemical properties of the lung membrane, thus leading to an increased pulmonary vascular permeability and structural failure of the alveolar cell membrane. In the present study, detailed molecular dynamic (MD) modeling was applied to investigate the effects of SO, NO, O and mixtures of these gases on the dipalmitoyl phosphatidylcholine (DPPC) phospholipid bilayer. The results showed that several key physical properties, including the mass density, lipid ordering parameter, lipid diffusion, and electrostatic potential of the cell membrane, have been changed by the binding of different compounds. This resulted in significant variations and more disorder in the DPPC bilayer. The multiple analyses of membrane properties proved the toxicity of NO, O, and SO to the DPPC bilayer, providing a theoretical basis for the experimental phenomenon that SO, NO and O can cause lung cell apoptosis. For the single systems, the damage to DPPC bilayer caused by O was more serious than NO and SO. More importantly, the MD simulations using the mixtures of SO, NO, and O showed a much greater decline of membrane fluidity and the aggravation of membrane damage than the single systems, indicating a synergistic effect when NO, SO, and O coexisted in the atmosphere, which could lead to much more severe damage and greater toxicities to the lung.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140547DOI Listing
November 2020

Formalin-induced and neuropathic pain altered time estimation in a temporal bisection task in rats.

Sci Rep 2019 12 10;9(1):18683. Epub 2019 Dec 10.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, P.R. China.

Time perception is an important ability that is related closely to humans' and animals' daily activities. It can be distorted by various emotional states. In human studies, experimental pain has been shown to prolong the perception of time. However, related animal studies are lacking. In this study, we used a temporal bisection task to investigate how acute inflammatory pain (induced by hind-paw formalin injection) and chronic neuropathic pain [induced by spinal nerve ligation (SNL)] affected time perception in rats. Rats were trained to recognize "short" (1200-ms) and "long" (2400-ms) anchor-duration pure tones and were rewarded for corresponding lever presses. During testing, rats perceived a series of intermediate-duration and anchor-duration pure tones, and selected levers corresponding to the "short" and "long" tones. After formalin injection, rats gave more "long" lever-press responses than after saline injection. The point of subjective equality after formalin injection also increased, suggesting that formalin-induced acute pain extended time perception. In contrast, rats that had undergone SNL gave fewer "long" lever-press responses compared with the sham surgery group. This animal study suggests that formalin-induced pain and neuropathic pain may have different effects on time perception.
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http://dx.doi.org/10.1038/s41598-019-55168-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904569PMC
December 2019

Scalable Synthesis of Micromesoporous Iron-Nitrogen-Doped Carbon as Highly Active and Stable Oxygen Reduction Electrocatalyst.

ACS Appl Mater Interfaces 2019 Oct 10;11(42):39263-39273. Epub 2019 Oct 10.

Institute for Energy Research, School of Chemistry and Chemical Engineering, Key Laboratory of Zhenjiang , Jiangsu University , Zhenjiang 212013 , P. R. China .

Micromesoporous metal-nitrogen-doped carbons have attracted incremental attention owning to their high activities for the electrocatalyzing oxygen reduction reaction (ORR). However, scalable synthesis of micromesoporous metal-nitrogen-doped carbons having superior electrocatalytic activity and stability remains a challenge. Here, an iron-nitrogen-doped carbon with highly electrocatalytic properties was simply prepared by ZnCl activation of an in situ polymerized iron-containing polypyrrole ([email protected]) at high temperature. High yields of polypyrrole (∼98 wt %) and iron-nitrogen-doped carbon (∼47 wt %) could be reached. The eutectic state of FeCl-ZnCl and its derived ZnFeO maskant played important roles in making micromesopores, scattering iron atoms, and trapping nitrogen atoms, leading to numerous micromesopore defects, a larger specific surface area, a more nitrogen doping content, and active sites for the material. The electrochemical tests and Zn-air battery measurements showed that the micromesoporous iron-nitrogen-doped carbon could achieve much positive onset and half-wave potentials at 0.98 and 0.90 V, respectively, as well as a large current density (6.06 mA/cm) and good cycling stability. The combination of the iron-nitrogen doping and micromesopore defects by the eutectic salt activation method provided an effective way to scalable synthesize iron-nitrogen-doped carbon as highly active and stable oxygen reduction electrocatalytsts.
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http://dx.doi.org/10.1021/acsami.9b10723DOI Listing
October 2019

Mild Hyperthermia-Enhanced Enzyme-Mediated Tumor Cell Chemodynamic Therapy.

ACS Appl Mater Interfaces 2019 Jul 19;11(26):23065-23071. Epub 2019 Jun 19.

The heterogeneity and diversity of tumors seriously attenuate the curative outcome of single treatment modes. Combined therapy has been demonstrated to be a promising candidate to enhance therapeutic efficacy compared with monotherapy. As an emerging therapeutic strategy, chemodynamic therapy (CDT) has drawn extensive attention in recent years. However, the therapeutic efficiency of CDT is still unsatisfying because the level of intracellular hydrogen peroxide (HO) restricts the production of hydroxyl radicals (OH). In this study, a novel curative strategy which combines glucose oxidase (GOx)-mediated FeO-based Fenton reaction and multiwalled carbon nanotube (MWNT)-produced mild hyperthermia enhancer is proposed, achieving a mild hyperthermia-enhanced enzyme-mediated tumor cell CDT. GOx can catalyze the conversion of glucose into gluconic acid and HO, which can elevate acidity in the tumor microenvironment and boost FeO-based Fenton reaction, producing a myriad of OH to induce tumor cell death. Furthermore, by using the theory that a temperature rise expedites the kinetics of a chemical reaction, producing a higher reaction rate and more resultants per unit time, we integrate MWNTs in this therapy system, which generate mild hyperthermia so as to accelerate the Fenton reaction for increasing the productivity of OH. Therefore, an amplified CDT can be realized. The therapy platform, mild hyperthermia-enhanced GOx-mediated CDT, provides an effective treatment for cancer and takes CDT a step further.
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http://dx.doi.org/10.1021/acsami.9b08257DOI Listing
July 2019

Exploring toxicity of perfluorinated compounds through complex network and pathway modeling.

J Biomol Struct Dyn 2020 Jun 8;38(9):2604-2612. Epub 2019 Jul 8.

School of Pharmacy, Lanzhou University, Lanzhou, China.

Perfluorinated compounds (PFCs) have serious impacts on human health, which could interfere with the body's signal pathways and affect the normal hormone balance of humans. PFCs were reported to bind to many proteins causing a series of biological effects. It was quite possible that the in vivo action of PFCs was not a single target or a single pathway, suggesting the toxic effect was due to the disturbance of protein or gene network, not limited to the modification of a single target protein or gene. Thus, a PFCs-targets interaction network was constructed and the significant differences in the characteristics of complex networks between the branched PFCs and linear PFCs were observed. A molecular dynamics simulation proved that binding ability of the branched PFCs to the target protein was much weaker than that of the linear PFCs, explaining why the branched PFCs presented significantly difference from the linear PFCs in terms of complex network characteristics. In addition, four target genes were identified as the central node genes of the network. The four target genes were proved to present certain influences on some diseases, which suggested a high correlation between PFCs to these diseases, including obesity, hepatocellular carcinoma and diabetes. The present work was helpful to develop new approaches to identify the key toxic targets of compounds and to explore the toxicity effects on pathways. AbbreviationsARandrogen receptorBPAbisphenol AESR1estrogen receptor 1ESR2estrogen receptor 2GLTPglycolipid transfer proteinHbFthe fetal hemoglobinHBG1hemoglobin subunit γ-1hERαhuman ERαHSD17B1hydroxysteroid 17-β dehydrogenase 1KEGGKenya encyclopedia of genes and genomesMDmolecular dynamics simulationPFCsperfluorinated compoundsPFOAperfluorooctanoic acidPFOSperfluorooctane sulfonatePOPspersistent organic pollutantsRMSDroot-mean-square deviationSHBGsex hormone binding globulinSPC/Eextended simple point charge modelTRthyroid hormone receptorCommunicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1637281DOI Listing
June 2020

Sibling astrocytes share preferential coupling via gap junctions.

Glia 2019 10 19;67(10):1852-1858. Epub 2019 Jun 19.

Instituto Cajal-CSIC, Molecular, Cellular and Developmental Neurobiology Department, Madrid, Spain.

Astrocytes are organized as communicating cellular networks where each cell is connected to others via gap junctions. These connections are not pervasive and there is evidence for the existence of subgroups composed by preferentially connected cells. Despite being unclear how these are established, we hypothesized lineage might contribute to the establishment of these subgroups. To characterize the functional coupling of clonally related astrocytes, we performed intracellular dye injections in clones of astrocytes labeled with the StarTrack method. This methodology revealed sibling astrocytes are preferentially connected when compared to other surrounding astrocytes. These results suggest the role of the developmental origin in the organization of astrocytes as intercellular networks.
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http://dx.doi.org/10.1002/glia.23662DOI Listing
October 2019

Reward Processing under Chronic Pain from the Perspective of "Liking" and "Wanting": A Narrative Review.

Pain Res Manag 2019 21;2019:6760121. Epub 2019 Apr 21.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.

The therapeutic goals of patients with chronic pain are not only to relieve pain but also to improve the quality of life. Chronic pain negatively affects various aspects of daily life, such as by decreasing the motivation to work and reward sensitivity, which may lead to difficulties in daily life or even unemployment. Human and animal studies have shown that chronic pain damages reward processing; the exploration of associated internal mechanisms may aid the development of treatments to repair this damage. Incentive salience theory, used widely to describe reward processing, divides this processing into "liking" (reward-induced hedonic sensory impact) and "wanting" (reward-induced motivation) components. It has been employed to explain pathological changes in reward processing induced by psychiatric disorders. In this review, we summarize the findings of studies of reward processing under chronic pain and examine the effects of chronic pain on "liking" and "wanting." Evidence indicates that chronic pain compromises the "wanting" component of reward processing; we also discuss the neural mechanisms that may mediate this effect. We hope that this review aids the development of therapies to improve the quality of life of patients with chronic pain.
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http://dx.doi.org/10.1155/2019/6760121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501242PMC
December 2019

Understanding the interaction of single-walled carbon nanotube (SWCNT) on estrogen receptor: A combined molecular dynamics and experimental study.

Ecotoxicol Environ Saf 2019 May 4;172:373-379. Epub 2019 Feb 4.

School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

Considering the large-scale production of diversified nanomaterials, it is paramount importance to unravel the structural details of interactions between nanoparticles and biological systems, and thus to explore the potential adverse impacts of nanoparticles. Estrogen receptors (ER) is one of the most important receptor of human reproductive system and the binding of carbon nanotubes to estrogen receptors was the possible trigger leading to the reproductive toxicity of carbon nanotubes. Thus, with single-walled carbon nanotube (SWCNT) treated as model nanomaterials, a combination of in vivo experiments, spectroscopy assay and molecular dynamic modeling was applied to help us unravel some important issues on the binding characterization between SWCNT and the ligand binding domain (LBD) of ER alpha (ERα). The fluorescence assay and molecular dynamics simulations together validated the binding of SWCNT to ERα, suggesting the possible molecular initiating event. As a consequence, SWCNT binding led to a conformational change on tertiary structure levels and hydrophobic interaction was recognized as the driving force governing the binding behavior between SWCNT and LBD of ERα. A in vivo process presented that the exposure of SWCNT increased ERα expression from 26.43 pg/ml to 259.01 pg/ml, suggesting a potential estrogen interference effects of SWCNT. Our study offers insight on the binding of SWCNT and ERα LBD at atomic level, helpful to accurately evaluate the potential health risks of SWCNT.
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http://dx.doi.org/10.1016/j.ecoenv.2019.01.101DOI Listing
May 2019

Cholinergic M receptors are involved in morphine-induced expression of behavioral sensitization by regulating dopamine function in the nucleus accumbens of rats.

Behav Brain Res 2019 03 5;360:128-133. Epub 2018 Dec 5.

Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing, China. Electronic address:

Repeated administration of morphine profoundly influences the dopaminergic and cholinergic systems in the nucleus accumbens [including the shell of the nucleus accumbens (NAcS)]. Further, dopamine release is regulated by the cholinergic system, especially the M receptor. Drug priming is one of the main factors that induces relapse in drug addiction. The present study first investigated how activation of the M receptor in the NAcS affects the expression of morphine-induced behavioral sensitization, through the administration of an M agonist (LY2033298) and antagonist (tropicamide), as well as a combination of an acetylcholinesterase inhibitor and M antagonist (huperzine-A + tropicamide). Additionally, the influence of a dopamine receptor agonist, in conjunction with an M agonist (i.e., SKF38393 + LY2033298), was also examined. Behavioral sensitization was established by exposure to 5 mg/kg morphine once every three days for a total of three exposures. The expression of behavioral sensitization was challenged by 5 mg/kg morphine. Results showed that (1) microinjection of the M receptor agonist LY2033298 (0.2 μg/side), but not the antagonist tropicamide (5, 10, or 20 μM/side) into the NAcS blocked the expression of behavioral sensitization; (2) tropicamide (20 μM/side) reversed the inhibition effect of huperzine-A on this behavior; and (3) SKF38393 (1 μg/side) reversed the inhibitory effect of LY2033298 on the expression of morphine-induced behavioral sensitization. These results suggest that the cholinergic M receptor in the NAcS plays an important role in the morphine-induced expression of behavioral sensitization through the regulation of dopamine function in rats.
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http://dx.doi.org/10.1016/j.bbr.2018.12.009DOI Listing
March 2019

The role of dopamine D- and D-like receptors related to muscarinic M receptors in impulsive choice in high-impulsive and low-impulsive rats.

Pharmacol Biochem Behav 2019 01 14;176:43-52. Epub 2018 Nov 14.

Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing 100048, China. Electronic address:

The non-selective muscarinic receptor agonist oxotremorine-M has been found to decrease impulsive choice in high-impulsive (HI) rats and increase impulsive choice in low-impulsive (LI) rats, but little is known about the muscarinic M receptor agonist N-desmethylclozapine (NDMC). This study investigated effects of NDMC on impulsive choice, and the effect of co-administration of NDMC with the dopamine D-like receptor antagonist SCH 23390 or D-like receptor antagonist raclopride on impulsive choice in HI and LI rats, characterized by basal levels of impulsive choice in a delay-discounting task. The results revealed that NDMC (1 and 2 mg/kg) significantly increased impulsive choice in HI, but not LI rats. SCH 23390 significantly promoted impulsive choice in HI rats at 0.01 mg/kg, and in LI rats at 0.0075 and 0.01 mg/kg. Moreover, SCH 23390 (0.005 and 0.0075 mg/kg) significantly inhibited the increase in impulsive choice induced by NDMC (1 mg/kg) in HI rats, whereas the increase in impulsive choice produced by SCH 23390 (0.0075 mg/kg) was significantly reversed by NDMC (1 mg/kg) in LI rats. Raclopride (0.04, 0.08, and 0.12 mg/kg) did not affect choice in both HI and LI rats, but significantly antagonized the increase in impulsive choice induced by NDMC (1 mg/kg) in HI rats. These findings suggest that D- and D-like receptors might be involved in different effects of the M receptor agonist on impulsive choice between HI and LI rats.
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http://dx.doi.org/10.1016/j.pbb.2018.11.005DOI Listing
January 2019

Exploring the membrane toxicity of decabromodiphenyl ethane (DBDPE): Based on cell membranes and lipid membranes model.

Chemosphere 2019 Feb 20;216:524-532. Epub 2018 Oct 20.

School of Pharmacy, Lanzhou University, Lanzhou, 730000, China. Electronic address:

Decabromodiphenyl ethane (DBDPE) is widely used in industry as an alternative to the decabromodiphenyl ether (BDEs). The large-scale use of DBDPE could lead to rapid growth of the human accumulation level of DBDPE. However, the biophysics of accumulation of DBDPE in cell membranes, as one of determinants of DBDPE metabolism is not clear. In the present study, detailed observations of cell lactate dehydrogenase (LDH) and reactive oxygen species (ROS) levels measurements proved that the DBDPE exposure to cell could result in significant cell membrane damage by concentration-dependent manners. The fluorescence anisotropy analysis supported the evidence that high concentration DBDPE bound decreased membrane fluidity significantly. Besides it, a detailed molecular dynamic (MD) simulation was approached to investigate the effects of DBDPE on the DPPC (dipalmitoyl phosphatidylcholine) phospholipid bilayer, which was constructed as the model of cell membrane. The molecular dynamic simulation revealed that DBDPE molecules can easily enter the membrane from the aqueous phase. Under the concentration of a threshold, the DBDPE molecules tended to aggregate inside the DPPC bilayer and caused pore formation. The bound of high concentration of DBDPE could result in significant variations in DPPC bilayer with a less dense, more disorder and rougher layer. The knowledge about DBDPEs interactions with lipid membranes is fundamentally essential to understand the in vivo process of DBDPE and the physical basis for the toxicity of DBDPE in cell membranes.
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http://dx.doi.org/10.1016/j.chemosphere.2018.10.140DOI Listing
February 2019

A sensitively non-enzymatic amperometric sensor and its application in living cell superoxide anion radical detection.

Talanta 2018 Aug 23;186:248-255. Epub 2018 Apr 23.

Key Laboratory of Bioelectrochemistry & Environmental Analysis of Gansu Province, College of Chemistry & Chemical Engineering, Northwest Normal University, Lanzhou 730070, PR China. Electronic address:

Here, we report a nanocomposite composed of silver nanoparticles and multi-walled carbon nanotubes (AgNPs/MWNTs) utilized as an efficient electrode material for sensitive detection superoxide anion (O). The procedure to synthesize AgNPs/MWNTs nanocomposites was green and facile. In the presence of functionalized multi-wall carbon nanotubes (MWNTs), silver nanoparticles (AgNPs) were in situ generated by chemical reduction of silver nitrate with glucose as a reducing and stabilizing agent to give the desired AgNPs/MWNTs nanocomposites. The nanocomposites can be easily used for the construction of an electrochemical sensor on glassy carbon electrode (GCE). The characterization of sensor and experimental parameters affecting its activity were investigated employing scanning electron microscopy (SEM), energy-dispersive X-ray spectrometer (EDS), X-ray diffraction (XRD), and cyclic voltammetry (CV). The resulted sensor exhibited favorable electrochemical performance for O sensing with a low detection limit of 0.1192 nM and wide linear range of 6 orders of magnitude, which guarantees the capacity of sensitive and credible detection of O released from living cells. Notably, a simulation experiment indicated the capacity to resist oxidative stress is limited in biological milieu. Thus this work has great potential for further applications in biological researches.
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http://dx.doi.org/10.1016/j.talanta.2018.04.067DOI Listing
August 2018

Muscarinic receptors in the nucleus accumbens shell play different roles in context-induced or morphine-challenged expression of behavioral sensitization in rats.

Eur J Pharmacol 2018 Jan 28;819:51-57. Epub 2017 Nov 28.

Beijing Key Laboratory of Learning and Cognition, Department of Psychology, Capital Normal University, Beijing, PR China. Electronic address:

Both drug-related cues and drug priming are the main factors that induce relapse of drug addiction. Previous research has reported that blockade of the muscarinic receptors could significantly depress addictive behavior, suggesting that the muscarinic receptors might be involved in drug use and relapse behavior. The nucleus accumbens (NAc), especially the shell of the NAc, where the muscarinic receptors are expressed, is critical for craving and relapse. This study investigated the effects of microinfusion of the muscarinic receptor antagonist scopolamine into the NAc shell on context- and morphine-induced expression of behavioral sensitization. Behavioral sensitization was established by exposure to 5mg/kg morphine once daily for five consecutive days. Expression of behavioral sensitization was induced by saline challenge or 5mg/kg morphine challenge. The results showed that: (a) the muscarinic receptor antagonist scopolamine (10.8μg/rat) microinjected into the NAc shell blocked expression of conditional sensitization; (b) acetylcholinesterase inhibitor huperzine-A (0.5 and 0.1μg/rat), but not scopolamine (10.8μg/rat), microinjected into the NAc shell blocked morphine-induced expression of sensitization; and (c) pre-infusion of scopolamine (10.8μg/rat) reversed the inhibitory effect of huperzine-A (0.5μg/rat) on morphine-induced sensitization. Our findings suggest that muscarinic receptors in the NAc shell play different roles in context-induced and morphine-challenged expression of behavioral sensitization.
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http://dx.doi.org/10.1016/j.ejphar.2017.11.039DOI Listing
January 2018

DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages.

Sci Rep 2017 06 12;7(1):3296. Epub 2017 Jun 12.

Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.

The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein (oxLDL) significantly enhanced DC-SIGN protein expression levels after a short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of interleukin 1-β (IL1-β), monocyte chemo-attractant protein 1 (MCP-1), tumor necrosis factor-α (TNFα) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the plasma membrane after oxLDL stimulation. The presence of an endogenous interaction and the results of the in vitro pull-down assays revealed that DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates TLR4-regulated NFκB activation but not activation of p38 and JNK. Our results suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the pathogenesis of atherosclerosis.
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http://dx.doi.org/10.1038/s41598-017-03740-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468253PMC
June 2017

Parecoxib increases muscle pain threshold and relieves shoulder pain after gynecologic laparoscopy: a randomized controlled trial.

J Pain Res 2016 13;9:653-660. Epub 2016 Sep 13.

Department of Obstetrics and Gynecology.

Objectives: Postlaparoscopic shoulder pain (PLSP) remains a common problem after laparoscopies. The aim of this study was to investigate the correlation between pressure pain threshold (PPT) of different muscles and PLSP after gynecologic laparoscopy, and to explore the effect of parecoxib, a cyclooxygenase-2 inhibitor, on the changes of PPT.

Materials And Methods: The patients were randomly allocated into two groups; group P and group C. In group P, parecoxib 40 mg was intravenously infused at 30 minutes before surgery and 8 and 20 hours after surgery. In group C, normal saline was infused at the corresponding time point. PPT assessment was performed 1 day before surgery and at postoperative 24 hours by using a pressure algometer at bilateral shoulder muscles (levator scapulae and supraspinatus) and forearm (flexor carpi ulnaris). Meanwhile, bilateral shoulder pain was evaluated through visual analog scale score at 24 hours after surgery.

Results: Preoperative PPT level of the shoulder, but not of the forearm, was significantly and negatively correlated with the intensity of ipsilateral PLSP. In group C, PPT levels of shoulder muscles, but not of forearm muscles, decreased after laparoscopy at postoperative 24 hours. The use of parecoxib significantly improved the decline of PPT levels of bilateral shoulder muscles (all <0.01). Meanwhile, parecoxib reduced the incidence of PLSP (group P: 45% vs group C: 83.3%; odds ratio: 0.164; 95% confidence interval: 0.07-0.382; <0.001) and the intensity of bilateral shoulder pain (both <0.01).

Conclusion: Preoperative PPT levels of shoulder muscles are closely associated with the severity of shoulder pain after gynecologic laparoscopy. PPT levels of shoulder muscles, but not of forearm muscles, significantly decreased after surgery. Parecoxib improved the decrease of PPT and relieved PLSP.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028176PMC
http://dx.doi.org/10.2147/JPR.S115889DOI Listing
September 2016

Impact of Astroglial Connexins on Modafinil Pharmacological Properties.

Sleep 2016 06 1;39(6):1283-92. Epub 2016 Jun 1.

Theranexus, Lyon, France.

Study Objectives: Modafinil is a non-amphetaminic wake-promoting compound used as therapy against sleepiness and narcolepsy. Its mode of action is complex, but modafinil has been recently proposed to act as a cellular-coupling enhancer in glial cells, through modulation of gap junctions constituted by connexins. The present study investigated in mice the impact of connexins on the effects of modafinil using connexin inhibitors.

Methods: Modafinil was administered alone or combined with inhibitors of astrocyte connexin, meclofenamic acid, or flecainide, respectively, acting on Cx30 and Cx43. Sleep-wake states were monitored in wild-type and narcoleptic orexin knockout mice. A spontaneous alternation task was used to evaluate working memory in wild-type mice. The effects of the compounds on astroglial intercellular coupling were determined using dye transfer in acute cortical slices.

Results: Meclofenamic acid had little modulation on the effects of modafinil, but flecainide enhanced the wake-promoting and pro-cognitive effects of modafinil. Co-administration of modafinil/flecainide resulted in a marked decrease in the number and duration of direct transitions to rapid eye movement sleep, which are characteristic of narcoleptic episodes in orexin knockout mice. Furthermore, modafinil enhanced the connexin-mediated astroglial cell coupling, whereas flecainide reduced it. Finally, this modafinil-induced effect was reversed by co-administration with flecainide.

Conclusions: Our study indicates that flecainide impacts the pharmacological effects of modafinil, likely through the normalization of Cx30-dependent gap junctional coupling in astroglial networks. The enhancement of the wake-promoting, behavioral, and cognitive outcomes of modafinil demonstrated here with flecainide would open new perspectives in the management of sleep disorders such as narcolepsy.

Commentary: A commentary on this article appears in this issue on page 1175.
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http://dx.doi.org/10.5665/sleep.5854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4863218PMC
June 2016

General anesthetics have differential inhibitory effects on gap junction channels and hemichannels in astrocytes and neurons.

Glia 2016 Apr 15;64(4):524-36. Epub 2015 Dec 15.

Collège De France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National De La Recherche Scientifique, Unité Mixte De Recherche 7241/Institut National De La Santé Et De La Recherche Médicale U1050, Paris Cedex 05, France.

Astrocytes represent a major non-neuronal cell population actively involved in brain functions and pathologies. They express a large amount of gap junction proteins that allow communication between adjacent glial cells and the formation of glial networks. In addition, these membrane proteins can also operate as hemichannels, through which "gliotransmitters" are released, and thus contribute to neuroglial interaction. There are now reports demonstrating that alterations of astroglial gap junction communication and/or hemichannel activity impact neuronal and synaptic activity. Two decades ago we reported that several general anesthetics inhibited gap junctions in primary cultures of astrocytes (Mantz et al., (1993) Anesthesiology 78(5):892-901). As there are increasing studies investigating neuroglial interactions in anesthetized mice, we here updated this previous study by employing acute cortical slices and by characterizing the effects of general anesthetics on both astroglial gap junctions and hemichannels. As hemichannel activity is not detected in cortical astrocytes under basal conditions, we treated acute slices with the endotoxin LPS or proinflammatory cytokines to induce hemichannel activity in astrocytes, which in turn activated neuronal hemichannels. We studied two extensively used anesthetics, propofol and ketamine, and the more recently developed dexmedetomidine. We report that these drugs have differential inhibitory effects on gap junctional communication and hemichannel activity in astrocytes when used in their respective, clinically relevant concentrations, and that dexmedetomidine appears to be the least effective on both channel functions. In addition, the three anesthetics have similar effects on neuronal hemichannels. Altogether, our observations may contribute to optimizing the selection of anesthetics for in vivo animal studies.
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http://dx.doi.org/10.1002/glia.22946DOI Listing
April 2016

[The relationship of SIRT3 with cellular metabolism and cardiovascular diseases].

Yi Chuan 2015 Feb;37(2):111-20

Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.

Protein deacetylases play an extremely crucial role in cellular biological processes and have been categorized into four families (HDACⅠ, HDACⅡ, HDACⅢ and HDACⅣ) in human. Of them, HDACⅢ, also known as the Sir2 (Silent information regulator 2) family, contains seven members, SIRT1-7, each exhibiting different cellular localization and biological function. As a major mitochondrial deacetylase, SIRT3 not only modulates cellular metabolism, but also plays important roles in apoptosis, tumor growth, aging and a number of other diseases. In this review, we summarize recent findings related to SIRT3 with an emphasis on its biological functions in regulating cell metabolism and its possible roles in cardiovascular diseases.
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http://dx.doi.org/10.16288/j.yczz.14-283DOI Listing
February 2015

Laryngeal mask airway does not reduce postoperative nasal bleeding outside the operation room after intranasal surgery.

ScientificWorldJournal 2013 28;2013:461023. Epub 2013 Nov 28.

Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510089, China.

Background: The aim of this study was to detect the effect of the laryngeal mask airway (LMA) versus the endotracheal tube (ETT) on postoperative nasal bleedings in and outside the operation room (OR) after intranasal surgery.

Methods: 134 patients undergoing elective intranasal surgeries were randomly allocated to receive LMA or ETT during general anesthesia. The incidence, episodes, and severity of nasal bleeding were evaluated in the OR and within the postoperative 24 hours in the ward. Furthermore, medical assistance and severe complications were assessed.

Results: THE overall incidence of postoperative nasal bleeding throughout the observation period was similar between the two groups. The LMA reduced nasal bleeding in the OR. However, outside the OR, the incidence of the first episode of postoperative nasal bleeding in the LMA group was higher than that in the ETT group (difference: -26.5%; 95% CI: -42.2% to -10.7%; P < 0.001). In the LMA group, more patients needed medical assistance (P = 0.029), and the number of assistance was also higher (P = 0.027) in the ward. No severe complications occurred during the observation period.

Conclusion: The LMA does not alleviate nasal bleeding conditions and even increases the demands of medical service outside the OR after intranasal surgery, although it reduces epistaxis during extubation.
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http://dx.doi.org/10.1155/2013/461023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864139PMC
July 2014

Effects of intraventricular methotrexate administration on Cuprizone-induced demyelination in mice.

Front Mol Neurosci 2013 16;6:34. Epub 2013 Oct 16.

Tisch MS Research Center of New York New York, NY, USA.

We previously showed that intrathecal administration of methotrexate slowed disability progression in multiple sclerosis (MS) patients with progressive disease. In general MS patients with progressive disease respond poorly to anti-inflammatory therapies. In order to better understand the mechanism by which methotrexate is protective in progressive MS, we analyzed its impact on the non-inflammatory cuprizone-induced demyelination model. When low-dose methotrexate was administered intracerebroventricularly it reduced demyelination and accumulation of GFAP+ reactive astrocytes in the corpus callosum. Administration of methotrexate after the withdrawal of cuprizone neither delayed remyelination nor influenced the number of astrocytes in the corpus callosum suggesting that methotrexate does not interfere with repair processes in the CNS. Moreover, methotrexate increased the expression of IGF1 in vitro and in vivo, a factor known to protect oligodendrocytes and limit the activation of astrocytes. Our studies show that methotrexate has an impact on pathogenic process in a demyelination model whose pathophysiological basis is not primarily related to inflammatory mechanisms, similar to neurodegenerative mechanisms associated with progressive MS. The pronounced inhibitory influence of methotrexate on the accumulation of astrocytes in the corpus callosum suggests that intrathecal methotrexate modulates astroglial activation in progressive MS possibly by promoting CNS production of IGF1.
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http://dx.doi.org/10.3389/fnmol.2013.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797440PMC
October 2013

The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes.

Neuropharmacology 2013 Dec 9;75:533-8. Epub 2013 May 9.

Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale Unité 1050, 75231 Paris Cedex 05, France; University Pierre et Marie Curie, ED, N°158, 75005 Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France. Electronic address:

Sleep-wake cycle is characterized by changes in neuronal network activity. However, for the last decade there is increasing evidence that neuroglial interaction may play a role in the modulation of sleep homeostasis and that astrocytes have a critical impact in this process. Interestingly, astrocytes are organized into communicating networks based on their high expression of connexins, which are the molecular constituents of gap junction channels. Thus, neuroglial interactions should also be considered as the result of the interplay between neuronal and astroglial networks. Here, we investigate the effect of modafinil, a wakefulness-promoting agent, on astrocyte gap junctional communication. We report that in the cortex modafinil injection increases the expression of mRNA and protein of connexin 30 but not those of connexin 43, the other major astroglial connexin. These increases are correlated with an enhancement of intercellular dye coupling in cortical astrocytes, which is abolished when neuronal activity is silenced by tetrodotoxin. Moreover, gamma-hydroxybutyric acid, which at a millimolar concentration induces sleep, has an opposite effect on astroglial gap junctions in an activity-independent manner. These results support the proposition that astroglia may play an important role in complex physiological brain functions, such as sleep regulation, and that neuroglial networking interaction is modified during sleep-wake cycle. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'.
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http://dx.doi.org/10.1016/j.neuropharm.2013.04.019DOI Listing
December 2013

From a glial syncytium to a more restricted and specific glial networking.

J Physiol Paris 2012 Jan 29;106(1-2):34-9. Epub 2011 Sep 29.

CIRB, CNRS UMR UMR7241/INSERM U1050, MEMOLIFE Laboratory of Excellence and Paris Science Lettre, Collège de France, University Pierre et Marie Curie, ED, N°158, 11 Place Marcelin Berthelot, 75005 Paris, France.

In the brain, glia represents the cell population that expresses the highest level of connexins, the membrane protein constituents of gap junction channels and hemichannels. This statement has initially led to propose the existence of a glial syncytium. Since then, functional studies have established that connexin channel-mediated communication between glial cells was more restricted and plastic that primarily thought. In particular, this is the case for astrocytes that form functional networks of communicating cells. Altogether these findings lead to reconsider the interaction between neurons and glia that should not be solely studied at the single cell level but also at a more integrated level as the interplay between neuronal circuits and glial networks.
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http://dx.doi.org/10.1016/j.jphysparis.2011.09.001DOI Listing
January 2012

Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis.

J Neurol Sci 2012 Feb 1;313(1-2):167-77. Epub 2011 Oct 1.

Multiple Sclerosis Research Center of New York, 521W. 57th St., 4th floor, New York, NY 10019, USA.

Multiple sclerosis (MS) is associated with irreversible disability in a significant proportion of patients. At present, there is no treatment to halt or reverse the progression of established disability. In an effort to develop cell therapy-based strategies for progressive MS, we investigated the pre-clinical efficacy of bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NPs) as an autologous source of stem cells. MSC-NPs consist of a subpopulation of bone marrow MSCs with neural progenitor and immunoregulatory properties, and a reduced capacity for mesodermal differentiation, suggesting that this cell population may be appropriate for clinical application in the CNS. We investigated whether MSC-NPs could promote repair and recovery after intrathecal injection into mice with EAE. Multiple injections of MSC-NPs starting at the onset of the chronic phase of disease improved neurological function compared to controls, whereas a single injection had no effect on disease scores. Intrathecal injection of MSC-NPs correlated with reduced immune cell infiltration, reduced area of demyelination, and increased number of endogenous nestin-positive progenitor cells in EAE mice. These observations suggest that MSC-NPs may influence the rate of repair through effects on endogenous progenitors in the spinal cord. This study supports the use of autologous MSC-NPs in MS patients as a means of promoting CNS repair.
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http://dx.doi.org/10.1016/j.jns.2011.08.036DOI Listing
February 2012

Foster mother care but not prenatal morphine exposure enhances cocaine self-administration in young adult male and female rats.

Dev Psychobiol 2007 Jul;49(5):463-73

Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann Bldg., 111. Bronx, New York 10461, USA.

The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11-18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration.
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http://dx.doi.org/10.1002/dev.20240DOI Listing
July 2007

A slow-onset, long-duration indanamine monoamine reuptake inhibitor as a potential maintenance pharmacotherapy for psychostimulant abuse: effects in laboratory rat models relating to addiction.

Neuropharmacology 2006 Oct 8;51(5):993-1003. Epub 2006 Aug 8.

Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Building C - Room 393, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.

Slow-onset, long-lasting dopamine reuptake blockers with reduced abuse potential have been suggested as maintenance therapies for cocaine addiction. We have synthesized a series of 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake inhibitors as candidates for such maintenance pharmacotherapy. The initial lead compound, the N,N-dimethyl analogue 30,640 was then subjected to testing in addiction-relevant animal models. Compound 30,640 (2 mg/kg i.p.) produced a pronounced slow-onset, long-lasting increase (300-400%) in extracellular nucleus accumbens dopamine levels, as measured by in vivo brain microdialysis in awake laboratory rats. Slow-onset, long-lasting decreases (40-80%) in the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and the serotonin metabolite 5-hydroxyindoleacetic acid were also seen. Compound 30,640 (3 or 5 mg/kg i.p.) also produced a significant (approximately 30%) slow-onset, long-lasting enhancement of electrical brain-stimulation reward, which was additive with that of cocaine (5 mg/kg i.p.). When given to cocaine-administering rats, 30,640 (2.5, 3, 5, or 10 mg/kg i.p.) significantly inhibited (30-60%) intravenous cocaine self-administration, with a pronounced long-lasting profile. In sum, 30,640 showed cocaine-like effects, but with a marked slow-onset, long-lasting profile. We conclude that the prodrug strategy employed in the design of 30,640 achieved its goal. We suggest that such compounds may be useful as maintenance pharmacotherapies for psychostimulant addiction.
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http://dx.doi.org/10.1016/j.neuropharm.2006.06.009DOI Listing
October 2006

Electrical and chemical stimulation of the basolateral complex of the amygdala reinstates cocaine-seeking behavior in the rat.

Psychopharmacology (Berl) 2003 Jul 24;168(1-2):75-83. Epub 2003 Jan 24.

Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.

Rationale: The basolateral complex of the amygdala (BLC) is part of a neural circuit that is activated in humans during cocaine craving elicited by exposure to drug-related environmental cues. In animals, the BLC is necessary for cocaine-seeking behavior elicited by cocaine-associated cues. It has not been determined whether BLC activation is sufficient to reinstate cocaine seeking.

Objectives: To determine whether electrical or excitatory amino-acid stimulation of the BLC is sufficient to induce reinstatement of cocaine seeking in rats.

Methods: Rats were catheterized and trained to lever-press for intravenous cocaine infusions on a fixed ratio (FR)-1 schedule of reinforcement. Once baseline cocaine-taking criteria were met, lever-pressing behavior was extinguished by substitution of saline for cocaine. After meeting criteria for extinction, animals were subjected to brief electrical (20 Hz, 400 microA or 2 Hz, 400 microA; 200 pulses per stimulation) or N-methyl- d-aspartate (NMDA; 250 ng/0.5 microl) BLC stimulation and lever pressing behavior was monitored. RESULTS. Electrical BLC stimulation with 20-Hz produced reinstatement of lever pressing previously associated with cocaine self-administration, while 2-Hz stimulation did not. Electrical stimulation of cerebellar and medial forebrain bundle loci did not reinstate cocaine seeking. Hence, the reinstatement was frequency dependent and anatomically selective. NMDA microinjections into the BLC also reinstated cocaine-seeking behavior.

Conclusions: BLC stimulation is sufficient to reinstate cocaine-seeking behavior in the rat. These results are congruent with the hypothesis that the basolateral complex of the amygdala is part of a neural system mediating drug-seeking behavior.
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http://dx.doi.org/10.1007/s00213-002-1328-3DOI Listing
July 2003

Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats.

J Neurosci 2002 Nov;22(21):9595-603

Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.

dopamine D3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6758043PMC
November 2002
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