Research Topics
Genomes and Genes | Uwe RudolphSummaryAffiliation: University of Zurich Country: Switzerland Publications
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Publications
Genetically modified animals in pharmacological research: future trendsU Rudolph
Institute of Pharmacology, Swiss Federal Institute of Technology ETH, University of Zurich
Eur J Pharmacol 375:327-37. 1999..Techniques which permit the time- and tissue-specific inducible regulation of gene expression present an important methodological advance...
Molecular and neuronal substrates for general anaestheticsUwe Rudolph
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Nat Rev Neurosci 5:709-20. 2004....
Identification of molecular substrate for the attenuation of anxiety: a step toward the development of better anti-anxiety drugsU Rudolph
Institute of Pharmacology and Toxicology, University of Zurich
ScientificWorldJournal 1:192-3. 2001..Benzodiazepines like diazepam bind to GABA(A) receptors containing the alpha subunits alpha 1, alpha 2, alpha 3, or alpha 5, most likely in alphabetagamma combinations...
Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse geneticsUwe Rudolph
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich
Annu Rev Pharmacol Toxicol 44:475-98. 2004....
GABA(A) receptor subtypes: dissecting their pharmacological functionsU Rudolph
Institute of Pharmacology and Toxicology, University of Zürich and Swiss Federal Institut of Technology ETH Zürich, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
Trends Pharmacol Sci 22:188-94. 2001..Such discoveries could open up new avenues for drug development...
Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypesU Rudolph
Institute of Pharmacology, University of Zurich, Switzerland
Nature 401:796-800. 1999..Thus, benzodiazepine-induced behavioural responses are mediated by specific GABA(A) receptor subtypes in distinct neuronal circuits, which is of interest for drug design...
Mapping the contribution of beta3-containing GABAA receptors to volatile and intravenous general anesthetic actionsAnja Zeller
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstr, 190, CH 8057 Switzerland
BMC Pharmacol 7:2. 2007..In this communication, we analyzed the contribution of beta3-containing GABAA receptors to the pharmacological actions of isoflurane, etomidate and propofol by means of beta3(N265M) mice...
Specific subtypes of GABAA receptors mediate phasic and tonic forms of inhibition in hippocampal pyramidal neuronsGeorge A Prenosil
University of Zurich, Institute of Pharmacology and Toxicology, Zurich, Switzerland
J Neurophysiol 96:846-57. 2006..These results show that the major forms of inhibitory neurotransmission in hippocampal pyramidal cells are mediated by distinct GABA(A)Rs subtypes...
The alpha5(H105R) mutation impairs alpha5 selective binding properties by altered positioning of the alpha5 subunit in GABAA receptors containing two distinct types of alpha subunitsEla Balic
Institute of Pharmacology and Toxicology, University of Zurich, Winterhurerstrasse, Zurich, Switzerland
J Neurochem 110:244-54. 2009..These findings imply an important role of histidine 105 in determining the position of the alpha5 subunit within the receptor complex by determining the affinity for assembly with the gamma2 subunit...
Requirement of alpha5-GABAA receptors for the development of tolerance to the sedative action of diazepam in miceCarolien van Rijnsoever
Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland
J Neurosci 24:6785-90. 2004..Thus, the chronic activation of alpha(5)-GABA(A) receptors is crucial for the normal development of sedative tolerance to diazepam, which manifests itself in conjunction with alpha1-GABA(A) receptors...
Mutational analysis of molecular requirements for the actions of general anaesthetics at the gamma-aminobutyric acidA receptor subtype, alpha1beta2gamma2Roberta Siegwart
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
BMC Pharmacol 3:13. 2003..We have now characterized the phenotypic effect of two beta subunit mutations in the most abundant GABA(A) receptor subtype, alpha1beta2gamma2...
Genuine antihyperalgesia by systemic diazepam revealed by experiments in GABAA receptor point-mutated miceJulia Knabl
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Pain 141:233-8. 2009..We conclude that systemic diazepam exerts a genuine antihyperalgesic effect, which depends on spinal GABA(A) receptors containing alpha2 and/or alpha3 subunits...
GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extractsDietmar Benke
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Neuropharmacology 56:174-81. 2009..In beta3 (N265M) point-mutated mice the anxiolytic activity of valerenic acid was absent. Thus, neurons expressing beta3 containing GABA(A) receptors are a major cellular substrate for the anxiolytic action of valerian extracts...
Spatiotemporal specificity of GABAA receptor-mediated regulation of adult hippocampal neurogenesisVenceslas Duveau
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Eur J Neurosci 34:362-73. 2011..Taken together, the availability of distinct GABA(A) R subtypes provides a molecular mechanism endowing spatiotemporal specificity to GABAergic control of neuronal maturation in adult brain...
Isoflurane-induced surgical tolerance mediated only in part by beta3-containing GABA(A) receptorsSachar Lambert
Institute of Pharmacology and Toxicology, , Winterthurerstrasse 190, , Switzerland
Eur J Pharmacol 516:23-7. 2005..At high concentrations isoflurane also immobilizes beta3(N265M) mice, indicating that other targets also mediate immobility. Thus, our findings support a multisite model for the immobilizing action of isoflurane...
Alteration of GABAergic synapses and gephyrin clusters in the thalamic reticular nucleus of GABAA receptor alpha3 subunit-null miceRemo Studer
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Eur J Neurosci 24:1307-15. 2006..The absence of GABAA-mediated transmission in the nRT may have a significant impact on the function of the thalamo-cortical loop of alpha3(0/0) mice...
Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofolAnja Zeller
Institute of Pharmacology and Toxicology, , Switzerland
FASEB J 19:1677-9. 2005....
alpha2-gamma-Aminobutyric acid (GABA)A receptors are the molecular substrates mediating precipitation of narcosis but not of sedation by the combined use of diazepam and alcohol in vivoMarcus Täuber
Institut of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Eur J Neurosci 18:2599-604. 2003....
Identification of a molecular target mediating the general anesthetic actions of pentobarbitalAnja Zeller
Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
Mol Pharmacol 71:852-9. 2007..In summary, we show a clear pharmacological dissociation of the immobilizing/hypnotic and respiratory/cardiovascular actions of pentobarbital...
Tonic inhibition in principal cells of the amygdala: a central role for α3 subunit-containing GABAA receptorsAnne Marowsky
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
J Neurosci 32:8611-9. 2012....
Presynaptic alpha2-GABAA receptors in primary afferent depolarization and spinal pain controlRobert Witschi
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
J Neurosci 31:8134-42. 2011..Our results thus show that part of the antihyperalgesic action of spinally applied DZP occurs through facilitated activation of GABA(A) receptors residing on primary nociceptors...
Regulation of cognition and symptoms of psychosis: focus on GABA(A) receptors and glycine transporter 1Hanns Mohler
University of Zurich and Swiss Federal Institute of Technology, Zurich, Institute of Pharmacology, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Pharmacol Biochem Behav 90:58-64. 2008..Taken together, these results qualify distinct GABA-A receptor subtypes and GlyT1 as molecular targets for the development of a new pharmacology in the treatment of cognitive decline and psychotic symptoms...
Analysis of the presence and abundance of GABAA receptors containing two different types of alpha subunits in murine brain using point-mutated alpha subunitsDietmar Benke
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057, Switzerland
J Biol Chem 279:43654-60. 2004..This experimental approach provides the basis for a detailed analysis of the abundance of GABAA receptors containing heterologous alpha subunits on a brain regional level...
General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunitRachel Jurd
Institute of Pharmacology and Toxicology, University of Zurich, CH 8057 Zurich, Switzerland
FASEB J 17:250-2. 2003....
GABA-based therapeutic approaches: GABAA receptor subtype functionsUwe Rudolph
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland, and Laboratory of Genetic Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
Curr Opin Pharmacol 6:18-23. 2006..Thus, a new pharmacology based on GABAA receptor subtype-specific actions is emerging...
Diazepam-induced adaptive plasticity revealed by alpha1 GABAA receptor-specific expression profilingLaura Huopaniemi
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
J Neurochem 88:1059-67. 2004..This long-term alteration is likely to contribute to the resetting of the neuronal responsiveness, which may be involved in rebound phenomena and, under chronic treatment, in the development of tolerance and dependence...
Dissecting the role of diazepam-sensitive γ-aminobutyric acid type A receptors in defensive behavioral reactivity to mild threatChristina Koester
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Pharmacol Biochem Behav 103:541-9. 2013..In the absence of these receptors, diazepam through activation of α1-GABA(A)Rs remains effective in reducing risk assessment, but not behavioral aversion...
Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3)gamma(2)gamma-aminobutyric acid(A) receptorsRoberta Siegwart
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
J Neurochem 80:140-8. 2002..The molecular switches induced by these mutations can be exploited to identify the molecular determinants for the action of general anesthetics...
Sleep EEG changes after zolpidem in miceCaroline Kopp
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, , Switzerland
Neuroreport 15:2299-302. 2004..We conclude that the effects of zolpidem on the sleep EEG in mice are distinct from the changes typically induced by benzodiazepines, and are primarily mediated by alpha1GABAA receptors...
Amino acid composition of brain cysts: levels of excitatory amino acids in cyst fluid fail to predict seizuresHeinz Gregor Wieser
Department of Neurology, University Hospital, University of Zurich, Frauenklinikstrasse 26, CH 8091 Zurich, Switzerland
Epilepsy Res 55:191-9. 2003..In summary, there is no evidence for a close correlation between excitatory amino acids in brain cysts and the occurrence of seizures...
Reversal of pathological pain through specific spinal GABAA receptor subtypesJulia Knabl
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen Nurnberg, D 91054 Erlangen, Germany
Nature 451:330-4. 2008..These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics...
Modulation of presynaptic beta3-containing GABAA receptors limits the immobilizing actions of GABAergic anestheticsChristian Grasshoff
Experimental Anesthesiology Section, Department of Anesthesiology and Intensive Care, Eberhard Karls University, Tuebingen, Germany
Mol Pharmacol 72:780-7. 2007....
Giant spontaneous depolarizing potentials in the developing thalamic reticular nucleusSusanne Pangratz-Fuehrer
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
J Neurophysiol 97:2364-72. 2007..Taken together, these data suggest that in immature nRt, long-lasting depolarizing responses mediated by GABA receptors could trigger Ca(2+) entry and play a role in functional development of the spindle-generating circuitry...
Dual actions of enflurane on postsynaptic currents abolished by the gamma-aminobutyric acid type A receptor beta3(N265M) point mutationBerthold Drexler
Department of Anesthesiology, Experimental Anesthesiology Section, University of Tuebingen, Germany
Anesthesiology 105:297-304. 2006..Furthermore, the role of the beta3 subunit in producing the depressant actions of enflurane on neocortical neurons was elucidated...
Diminished GABA(A) receptor-binding capacity and a DNA base substitution in a patient with treatment-resistant depression and anxietyMarkus Kosel
Psychiatric Neuroimaging Group of the Department of Psychiatry, University Hospital, Bern, Switzerland
Neuropsychopharmacology 29:347-50. 2004..No conclusion can, however, be made about casual links in this single case [corrected]...
Specific GABAA circuits for visual cortical plasticityMichela Fagiolini
Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2 1 Hirosawa, Wako Shi, Saitama, 351 0198 Japan
Science 303:1681-3. 2004..This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants...
Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclassesAlberto Bacci
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA
J Neurosci 23:9664-74. 2003..Moreover, selective pharmacological manipulation of distinct inhibitory circuits might allow regulation of pyramidal cell activities under specific physiological and pathophysiological conditions...
Etomidate and propofol-hyposensitive GABAA receptor beta3(N265M) mice show little changes in acute alcohol sensitivity but enhanced tolerance and withdrawalCarles Sanchis-Segura
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany
Neurosci Lett 416:275-8. 2007..The results of the present study suggest that the alcohol effects abolished by the beta3(N265M) mutation do not play a dominant role in acute alcohol intoxication but influence ethanol tolerance and withdrawal...
Dynamic GABA(A) receptor subtype-specific modulation of the synchrony and duration of thalamic oscillationsVikaas S Sohal
Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305-5122, USA
J Neurosci 23:3649-57. 2003..These results not only identify a particular anatomical and molecular target for anti-absence drug design, but also elucidate a specific dynamic mechanism by which inhibitory networks control neural oscillations...
Beta3-containing gamma-aminobutyric acidA receptors are not major targets for the amnesic and immobilizing actions of isofluraneMark Liao
Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143-0464, USA
Anesth Analg 101:412-8, table of contents. 2005....
R (+) etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the gamma-aminobutyric acid receptor beta3 subunitMark Liao
Department of Anesthesia and Perioperative Care, S-455, University of California, San Francisco, CA 94143-0464, USA
Anesth Analg 101:131-5, table of contents. 2005..6 +/- 1.5 min and 7.2 +/- 1.8 min, respectively), emphasizing the contribution of this residue as a determinant of a behavioral response of azietomidate in mice...
Propofol's effects on nociceptive behavior and spinal c-fos expression after intraplantar formalin injection in mice with a mutation in the gamma-aminobutyric acid-type(A) receptor beta3 subunitAustin W Merrill
Section of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California 95616, USA
Anesth Analg 103:478-83, table of contents. 2006..These data indicate that although propofol produces anesthesia, it does not prevent the FLI that is associated with nociception, a finding consistent with propofol lacking analgesic properties...
GABA receptors containing the alpha5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fearBenjamin K Yee
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH 8603 Schwerzenbach, Switzerland
Eur J Neurosci 20:1928-36. 2004..Our results identify neuronal inhibition in the hippocampus mediated via alpha5 GABAA receptors as a critical control element in the regulation of the acquisition and expression of associative memory...
Mouse gene knockout and knockin strategies in application to alpha subunits of Gi/Go family of G proteinsMeisheng Jiang
Department of Anesthesiology, School of Medicine, University of California, Los Angeles, California 90095, USA
Methods Enzymol 344:277-98. 2002
Intrinsic and synaptic dynamics interact to generate emergent patterns of rhythmic bursting in thalamocortical neuronsVikaas S Sohal
Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305-5122, USA
J Neurosci 26:4247-55. 2006..These results demonstrate that rhythmic PIR activity is an emergent property of interactions between intrinsic and synaptic currents, not just a passive reflection of incoming synaptic inhibition...
Opposing actions of etomidate on cortical theta oscillations are mediated by different gamma-aminobutyric acid type A receptor subtypesBerthold Drexler
Department of Anesthesiology, Section of Experimental Anesthesiology, University of Tuebingen, Tuebingen, Germany
Anesthesiology 102:346-52. 2005..The authors ask how etomidate, acting predominantly via gamma-aminobutyric acid type A (GABAA) receptors containing beta2 or beta3 subunits, affects theta activity in vitro...
