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Article: Naturally occurring variants in catecholamine receptor genes.

Insel, Paul A / Kirstein, Shelli L

2003 Volume 23, Issue 4, Page(s) 228–230

MeSH term(s)	Animals ; Genetic Variation/genetics ; Humans ; Receptors, Catecholamine/chemistry ; Receptors, Catecholamine/genetics ; Receptors, Catecholamine/metabolism
Chemical Substances	Receptors, Catecholamine
Language	English
Publishing date	2003-08
Publishing country	England
Document type	Lectures ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2090847-7
ISSN	1474-8673 ; 1474-8665
ISSN (online)	1474-8673
ISSN	1474-8665
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Article: Autonomic nervous system pharmacogenomics: a progress report.

Kirstein, Shelli L / Insel, Paul A

Pharmacological reviews

2004 Volume 56, Issue 1, Page(s) 31–52

Abstract: Pharmacogenetics, the inherited basis for interindividual differences in drug response, has rapidly expanded with the advent of new molecular tools and the sequencing of the human genome, yielding pharmacogenomics. We review here recent ideas and ... ...

Abstract	Pharmacogenetics, the inherited basis for interindividual differences in drug response, has rapidly expanded with the advent of new molecular tools and the sequencing of the human genome, yielding pharmacogenomics. We review here recent ideas and findings regarding pharmacogenomics of components of the autonomic nervous system, in particular, neuronal nicotinic acetylcholine receptors, postsynaptic receptors with which the parasympathetic and sympathetic neurotransmitters, acetylcholine (ACh) and norepinephrine, respectively, interact. The receptor subtypes that mediate these responses, M(1-3) muscarinic cholinergic receptors (mAChRs), and alpha(1A,B,D)-, alpha(2A,B,C)-, and beta(1,2,3)-adrenergic receptors (AR), show highly variable expression of genetic variants; variants of mAChRs and alpha(1)-ARs are relatively rare, whereas alpha(2)-AR and beta-AR subtype variants are quite common. The largest amount of data is available regarding variants of the latter ARs and represents efforts to associate certain receptor genotypes, most commonly, single nucleotide polymorphisms, with particular phenotypes (e.g., cardiovascular and metabolic responses). In vitro and in vivo studies have yielded inconsistent results; definitive conclusions are limited. We identify several conceptual and methodological problems with available data: sample size, ethnicity, tissue differences, coding versus noncoding variants, limited studies of haplotypes, and interaction among variants. Thus, although progress has been made in identifying genetic variation that influences drug response fo autonomic nervous system components, we are still at the early stages of defining the most critical genetic determinants and their role in human physiology and pharmacology.
MeSH term(s)	Animals ; Autonomic Nervous System/drug effects ; Autonomic Nervous System/metabolism ; Autonomic Nervous System/physiology ; Humans ; Pharmacogenetics/methods ; Pharmacogenetics/trends ; Polymorphism, Genetic/drug effects ; Receptors, Adrenergic/genetics ; Receptors, Adrenergic/physiology
Chemical Substances	Receptors, Adrenergic
Language	English
Publishing date	2004-03
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	209898-2
ISSN	1521-0081 ; 0031-6997
ISSN (online)	1521-0081
ISSN	0031-6997
DOI	10.1124/pr.56.1.2
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Article ; Online: Kinetic cell-based morphological screening: prediction of mechanism of compound action and off-target effects.

Abassi, Yama A / Xi, Biao / Zhang, Wenfu / Ye, Peifang / Kirstein, Shelli L / Gaylord, Michelle R / Feinstein, Stuart C / Wang, Xiaobo / Xu, Xiao

Chemistry & biology

2009 Volume 16, Issue 7, Page(s) 712–723

Abstract: We describe a cell-based kinetic profiling approach using impedance readout for monitoring the effect of small molecule compounds. This noninvasive readout allows continuous sampling of cellular responses to biologically active compounds and the ensuing ... ...

Abstract	We describe a cell-based kinetic profiling approach using impedance readout for monitoring the effect of small molecule compounds. This noninvasive readout allows continuous sampling of cellular responses to biologically active compounds and the ensuing kinetic profile provides information regarding the temporal interaction of compounds with cells. The utility of this approach was tested by screening a library containing FDA approved drugs, experimental compounds, and nature compounds. Compounds with similar activity produced similar impedance-based time-dependent cell response profiles (TCRPs). The compounds were clustered based on TCRP similarity. We identified novel mechanisms for existing drugs, confirmed previously reported calcium modulating activity for COX-2 inhibitor celecoxib, and identified an additional mechanism for the experimental compound monastrol. We also identified and characterized a new antimitotic agent. Our findings indicate that the TCRP approach provides predictive mechanistic information for small molecule compounds.
MeSH term(s)	Cluster Analysis ; Drug Discovery/methods ; Drug Evaluation, Preclinical/methods ; Electric Impedance ; Electrodes ; Kinetics ; Small Molecule Libraries/pharmacology
Chemical Substances	Small Molecule Libraries
Language	English
Publishing date	2009-06-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	917827-2
ISSN	1879-1301 ; 1074-5521
ISSN (online)	1879-1301
ISSN	1074-5521
DOI	10.1016/j.chembiol.2009.05.011
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Article ; Online: Cloning, expression, and functional analysis of rhesus monkey trace amine-associated receptor 6: evidence for lack of monoaminergic association.

Xie, Zhihua / Vallender, Eric J / Yu, Naichen / Kirstein, Shelli L / Yang, Hong / Bahn, Mary E / Westmoreland, Susan V / Miller, Gregory M

Journal of neuroscience research

2008 Volume 86, Issue 15, Page(s) 3435–3446

Abstract: Several recent studies report an association between trace amine-associated receptor 6 (TAAR6) and susceptibility to schizophrenia and bipolar affective disorder in humans. However, endogenous TAAR6 agonists and the receptor signaling profile and brain ... ...

Abstract	Several recent studies report an association between trace amine-associated receptor 6 (TAAR6) and susceptibility to schizophrenia and bipolar affective disorder in humans. However, endogenous TAAR6 agonists and the receptor signaling profile and brain distribution remain unclear. Here, we clone TAAR6 from the rhesus monkey and use transfected cells to investigate whether this receptor interacts with brain monoamines and a psychostimulant drug to trigger cAMP signaling or extracellular signal-regulated kinase (ERK) phosphorylation, while investigating its expression profile in the rhesus monkey brain. Unlike TAAR1, rhesus monkey TAAR6 did not alter cAMP levels in response to 10 microM of monoamines (dopamine, norepinephrine, serotonin, beta-phenylethylamine (beta-PEA), octopamine, tryptamine, and tyramine) or methamphetamine in stably transfected cells in vitro. Real-time cell electronic sensing analysis indicated that the receptor did not alter cell impedance or change the effect of forskolin on cell impedance at exposure to 20 microM of each monoamine, suggesting a lack of either Gs or Gi-linked signaling. Whereas kappa opioid receptor activation led to ERK phosphorylation at exposure to 1 microM U69593, rhesus monkey TAAR6 had no such effect at exposure to 10 microM of monoamines or methamphetamine. Membrane and cell surface localization of TAAR6 was confirmed by immunocytochemistry, biotinylation, and Western blot testing with a TAAR6 antibody in the transfected cells. Real-time reverse transcriptase-polymerase chain reaction amplification showed that TAAR6 mRNA was undetectable in selected rhesus monkey brain regions. Together, the data reveal that TAAR6 is unresponsive to brain monoamines and is not expressed in rhesus monkey brain monoaminergic nuclei, suggesting TAAR6 lacks direct association with brain monoaminergic neuronal function.
MeSH term(s)	Amino Acid Sequence ; Animals ; Biogenic Monoamines/pharmacology ; Blotting, Western ; Brain/drug effects ; Brain/metabolism ; Cloning, Molecular ; Cyclic AMP/metabolism ; Dopamine Agents/pharmacology ; Gene Expression ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Macaca mulatta ; Methamphetamine/pharmacology ; Molecular Sequence Data ; Receptors, G-Protein-Coupled/drug effects ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/physiology ; Transfection
Chemical Substances	Biogenic Monoamines ; Dopamine Agents ; Receptors, G-Protein-Coupled ; Methamphetamine (44RAL3456C) ; Cyclic AMP (E0399OZS9N)
Language	English
Publishing date	2008-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.21783
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Article: Dynamic and label-free cell-based assays using the real-time cell electronic sensing system.

Atienza, Josephine M / Yu, Naichen / Kirstein, Shelli L / Xi, Biao / Wang, Xiaobo / Xu, Xiao / Abassi, Yama A

Assay and drug development technologies

2006 Volume 4, Issue 5, Page(s) 597–607

Abstract: Cell-based assays have become an integral part of the preclinical drug development process. Recently, noninvasive label-free cell-based assay technologies have taken center stage, offering important and distinct advantages over and in addition to ... ...

Abstract	Cell-based assays have become an integral part of the preclinical drug development process. Recently, noninvasive label-free cell-based assay technologies have taken center stage, offering important and distinct advantages over and in addition to traditional label-based endpoint assays. Dynamic monitoring of live cells, the preclusion of label, and kinetics are some of the fundamental features of cell-based label-free technologies. In this article we will discuss the real-time cell electronic sensing (RT-CES, ACEA Biosciences Inc., San Diego, CA) system and some of its key applications for cell-based assays such as cell proliferation and cytotoxicity, functional assays for receptor-ligand analysis, cell adhesion and spreading assays, dynamic monitoring of endothelial barrier function, and dynamic monitoring of cell migration and invasion. Also, where appropriate we will briefly discuss other label-free technologies in an application-specific manner.
MeSH term(s)	Biological Assay/instrumentation ; Biological Assay/methods ; Biosensing Techniques/instrumentation ; Biosensing Techniques/methods ; Computer Systems ; Drug Design ; Electrochemistry/instrumentation ; Electrochemistry/methods ; Pharmacology/instrumentation ; Pharmacology/methods ; Staining and Labeling ; Technology Assessment, Biomedical ; Technology, Pharmaceutical/instrumentation ; Technology, Pharmaceutical/methods
Language	English
Publishing date	2006-10
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1540-658X
ISSN	1540-658X
DOI	10.1089/adt.2006.4.597
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Article: Live cell quality control and utility of real-time cell electronic sensing for assay development.

Kirstein, Shelli L / Atienza, Josephine M / Xi, Biao / Zhu, Jenny / Yu, Naichen / Wang, Xiaobo / Xu, Xiao / Abassi, Yama A

Assay and drug development technologies

2006 Volume 4, Issue 5, Page(s) 545–553

Abstract: In this paper we have explored the utility of the real-time cell electronic sensing (RTCES, ACEA Biosciences Inc., San Diego, CA) system for monitoring the quality of live cells in cell-based assays as well as for assay development. We have demonstrated ... ...

Abstract	In this paper we have explored the utility of the real-time cell electronic sensing (RTCES, ACEA Biosciences Inc., San Diego, CA) system for monitoring the quality of live cells in cell-based assays as well as for assay development. We have demonstrated that each cell type displays unique growth kinetic profiles that provide a quantitative account of cell behavior and can be used as a diagnostic tool for cellular quality control. The utility of the specific signature patterns was shown by demonstrating the significant differences in primary cell behavior depending on the supplier. In addition, the RT-CES system was able to differentiate cell behavior depending on the passage stage of the cells. The utility of the RT-CES system as an assay development tool was demonstrated in cytotoxicity assays. The RT-CES system not only provides information regarding the potency of cytotoxic compounds, but in addition relates potency to the rate of the response for each concentration of the compound tested, which is important for understanding the mechanism of compound action. Moreover, real-time display of cytotoxicity data by the RT-CES system allows for calculation of real-time 50% inhibitory concentration (IC50) values or determination of optimal IC(50) value. In summary, the RT-CES system provides high content and information-rich data that are beyond the scope of single-point assays.
MeSH term(s)	Biological Assay/instrumentation ; Biological Assay/methods ; Biosensing Techniques/instrumentation ; Biosensing Techniques/methods ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Computer Systems ; Cytotoxins/toxicity ; Electronics ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Endothelial Cells/physiology ; Humans ; Quality Control ; Toxicity Tests/instrumentation ; Toxicity Tests/methods
Chemical Substances	Cytotoxins
Language	English
Publishing date	2006-10
Publishing country	United States
Document type	Evaluation Studies ; Journal Article
ISSN	1540-658X
ISSN	1540-658X
DOI	10.1089/adt.2006.4.545
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Article ; Online: Coordinate down-regulation of adenylyl cyclase isoforms and the stimulatory G protein (G(s)) in intestinal epithelial cell differentiation.

Choi, Lillian J / Jenikova, Gabriela / Hanson, Elaine / Spehlmann, Martina E / Boehling, Nicholas S / Kirstein, Shelli L / Bundey, Richard A / Smith, Jennifer R / Insel, Paul A / Eckmann, Lars

The Journal of biological chemistry

2010 Volume 285, Issue 17, Page(s) 12504–12511

Abstract: The intestinal epithelium is dynamic, with proliferation of undifferentiated crypt cells balanced by terminal differentiation and cell death at the colon surface or small intestinal villus tips. Cyclic AMP, induced by agonists such as prostaglandin E(2) ... ...

Abstract	The intestinal epithelium is dynamic, with proliferation of undifferentiated crypt cells balanced by terminal differentiation and cell death at the colon surface or small intestinal villus tips. Cyclic AMP, induced by agonists such as prostaglandin E(2) and vasoactive intestinal polypeptide, promotes proliferation and ion secretion and suppresses apoptosis in intestinal epithelial cells. Here, we show that cell differentiation in a model intestinal epithelium leads to attenuation of cAMP production in response to G protein-coupled receptor and receptor-independent agonists. Concomitantly, key components of the cAMP cascade, the alpha subunit of the stimulatory G protein, G(s), and adenylyl cyclase (AC) isoforms 3, 4, 6, and 7 are down-regulated. By contrast, AC1, AC2, AC8, and AC9, and the receptors for prostaglandin E(2) and vasoactive intestinal polypeptide, are not expressed or not affected by differentiation. We confirmed key findings in normal murine colon epithelium, in which the major AC isoforms and G(s)alpha are markedly down-regulated in differentiated surface cells. Suppression of AC isoforms and G(s)alpha is functionally important, because their constitutive expression completely reverses differentiation-induced cAMP attenuation. Thus, down-regulation of AC isoforms and G(s)alpha is an integral part of the intestinal epithelial differentiation program, perhaps serving to release cells from cAMP-promoted anti-apoptosis as a prerequisite for cell death upon terminal differentiation.
MeSH term(s)	Adenylyl Cyclases/biosynthesis ; Animals ; Cell Differentiation/physiology ; Cell Line ; Colon/enzymology ; Dinoprostone/metabolism ; Down-Regulation/physiology ; Epithelial Cells/enzymology ; GTP-Binding Proteins/metabolism ; Gene Expression Regulation, Enzymologic/physiology ; Humans ; Intestinal Mucosa/enzymology ; Isoenzymes/biosynthesis
Chemical Substances	Isoenzymes ; GTP-Binding Proteins (EC 3.6.1.-) ; Adenylyl Cyclases (EC 4.6.1.1) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2010-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M109.059741
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Article: Coordinate Down-regulation of Adenylyl Cyclase Isoforms and the Stimulatory G Protein (Gs) in Intestinal Epithelial Cell Differentiation

Choi, Lillian J / Jenikova, Gabriela / Hanson, Elaine / Spehlmann, Martina E / Boehling, Nicholas S / Kirstein, Shelli L / Bundey, Richard A / Smith, Jennifer R / Insel, Paul A / Eckmann, Lars

Journal of biological chemistry. 2010 Apr. 23, v. 285, no. 17

2010

Abstract	The intestinal epithelium is dynamic, with proliferation of undifferentiated crypt cells balanced by terminal differentiation and cell death at the colon surface or small intestinal villus tips. Cyclic AMP, induced by agonists such as prostaglandin E₂ and vasoactive intestinal polypeptide, promotes proliferation and ion secretion and suppresses apoptosis in intestinal epithelial cells. Here, we show that cell differentiation in a model intestinal epithelium leads to attenuation of cAMP production in response to G protein-coupled receptor and receptor-independent agonists. Concomitantly, key components of the cAMP cascade, the α subunit of the stimulatory G protein, Gs, and adenylyl cyclase (AC) isoforms 3, 4, 6, and 7 are down-regulated. By contrast, AC1, AC2, AC8, and AC9, and the receptors for prostaglandin E₂ and vasoactive intestinal polypeptide, are not expressed or not affected by differentiation. We confirmed key findings in normal murine colon epithelium, in which the major AC isoforms and Gsα are markedly down-regulated in differentiated surface cells. Suppression of AC isoforms and Gsα is functionally important, because their constitutive expression completely reverses differentiation-induced cAMP attenuation. Thus, down-regulation of AC isoforms and Gsα is an integral part of the intestinal epithelial differentiation program, perhaps serving to release cells from cAMP-promoted anti-apoptosis as a prerequisite for cell death upon terminal differentiation.
Language	English
Dates of publication	2010-0423
Size	p. 12504-12511.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article: Quantitative trait loci affecting initial sensitivity and acute functional tolerance to ethanol-induced ataxia and brain cAMP signaling in BXD recombinant inbred mice.

Kirstein, Shelli L / Davidson, Kirsten L / Ehringer, Marissa A / Sikela, James M / Erwin, V Gene / Tabakoff, Boris

The Journal of pharmacology and experimental therapeutics

2002 Volume 302, Issue 3, Page(s) 1238–1245

Abstract: In previous work, we identified genetic correlations between cAMP accumulation in the cerebellum and sensitivity to the incoordinating effects of ethanol. A genetic correlation suggests that common genes underlie the phenotypes investigated. One method ... ...

Abstract	In previous work, we identified genetic correlations between cAMP accumulation in the cerebellum and sensitivity to the incoordinating effects of ethanol. A genetic correlation suggests that common genes underlie the phenotypes investigated. One method for provisionally identifying genes involved in a given phenotypic measure is quantitative trait locus (QTL) analysis. Using a panel of 30 BXD recombinant inbred strains of mice and the progenitors (DBA/2J and C57BL/6J), and the dowel test for ataxia, we measured the blood ethanol concentrations at the time an animal first fell from the dowel and acute functional tolerance (AFT), and investigated cAMP signaling in the cerebellum. Cyclic AMP accumulation was measured in whole-cell preparations of cerebellar minces from individual mice under basal or stimulated conditions. We conducted a genome-wide QTL analysis of the behavioral and biochemical measures with >2000 genetic markers to identify significant associations. Western blot and comparative sequencing analysis were used to compare cAMP response element binding protein (CREB) levels and protein-coding sequence, respectively. QTL analyses correlating strain means with allelic status at genetic markers identified several significant associations (p < 0.01). Analysis of variance revealed an effect of strain on behavioral and biochemical measures. There was a significant genetic correlation between initial sensitivity and basal cAMP accumulation in the cerebellum. We identified 6 provisional QTLs for initial sensitivity on four chromosomes, 6 provisional QTLs for AFT on four chromosomes, and 11 provisional QTLs for cAMP signaling on nine chromosomes. Two loci were found to overlap for measures of initial sensitivity and for cAMP signaling. Given the genetic correlation between initial sensitivity and basal cAMP accumulation, we investigated candidate genes in a QTL on chromosome 1. Comparative sequence analysis was performed, and protein levels were compared between C57 and DBA mice for Creb1. No significant differences were detected in coding sequence or protein levels for CREB. These results suggest that although ethanol sensitivity and cAMP signaling are determined by multiple genes, they may share certain genetic codetermination.
MeSH term(s)	Adrenergic beta-Agonists/pharmacology ; Animals ; Ataxia/chemically induced ; Ataxia/genetics ; Ataxia/psychology ; Blotting, Western ; Brain Chemistry/drug effects ; Central Nervous System Depressants/blood ; Central Nervous System Depressants/pharmacology ; Colforsin/pharmacology ; Cyclic AMP/physiology ; Cyclic AMP Response Element-Binding Protein/genetics ; Cyclic AMP Response Element-Binding Protein/metabolism ; DNA, Complementary/genetics ; Drug Tolerance ; Ethanol/blood ; Ethanol/pharmacology ; Isoproterenol/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Postural Balance/drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/drug effects ; Signal Transduction/genetics
Chemical Substances	Adrenergic beta-Agonists ; Central Nervous System Depressants ; Cyclic AMP Response Element-Binding Protein ; DNA, Complementary ; Colforsin (1F7A44V6OU) ; Ethanol (3K9958V90M) ; Cyclic AMP (E0399OZS9N) ; Isoproterenol (L628TT009W)
Language	English
Publishing date	2002-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.302.3.1238
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Article: Chronic ethanol exposure during adolescence increases basal dopamine in the nucleus accumbens septi during adulthood.

Badanich, Kimberly A / Maldonado, Antoniette M / Kirstein, Cheryl L

Alcoholism, clinical and experimental research

2007 Volume 31, Issue 5, Page(s) 895–900

Abstract: ... from PND 51 to 65. Changes in extracellular DA levels in the anterior NAcc shell were measured via the no ...

Abstract	Background: In humans, adolescent exposure to alcohol is associated with the onset of adult alcohol dependency and suggests that early use potentiates vulnerability to addiction. The aim of the present study was to address whether chronic ethanol exposure during adolescence would alter nucleus accumbens septi (NAcc) dopamine (DA) levels in the adult brain. Methods: Rats were injected daily from postnatal day (PND) 30 to 50 with either 0.75 g/kg/i.p. ethanol or saline followed by an ethanol-abstinent period from PND 51 to 65. Changes in extracellular DA levels in the anterior NAcc shell were measured via the no net flux (NNF) paradigm. Results: Extracellular DA levels were greater in rats chronically treated with ethanol during adolescence (6.5 nM DA) in comparison with saline-exposed controls (3.6 nM DA). There were no differences in extraction fraction (E(d)), an indirect measure of DA reuptake, between ethanol-treated (87%) and nontreated (68%) rats. Conclusions: Together these findings suggest that changes in extracellular DA may be an underlying physiological mechanism in adolescent vulnerability to the rewarding properties of ethanol.
MeSH term(s)	Aging/metabolism ; Alcoholism/metabolism ; Animals ; Dopamine/metabolism ; Extracellular Space/drug effects ; Extracellular Space/metabolism ; Limbic System/drug effects ; Limbic System/metabolism ; Limbic System/physiology ; Male ; Microdialysis ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/growth & development ; Nucleus Accumbens/metabolism ; Rats ; Rats, Sprague-Dawley ; Regression Analysis
Chemical Substances	Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2007-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/j.1530-0277.2007.00370.x
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