Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 6 October 2000:
Vol. 290. no. 5489, pp. 131 - 134
DOI: 10.1126/science.290.5489.131
Prev | Table of Contents | Next

Reports

Molecular and Neuronal Substrate for the Selective Attenuation of Anxiety

Karin Löw,1*dagger Florence Crestani,1* Ruth Keist,1* Dietmar Benke,1 Ina Brünig,1 Jack A. Benson,1 Jean-Marc Fritschy,1 Thomas Rülicke,2 Horst Bluethmann,3 Hanns Möhler,1 Uwe Rudolph1ddagger

Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the alpha 2 or alpha 3 GABAA (gamma -aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the alpha 2(H101R) point mutation but present in mice with the alpha 3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha 2 GABAA receptors, which are largely expressed in the limbic system, but not by alpha 3 GABAA receptors, which predominate in the reticular activating system.

1 Institute of Pharmacology and Toxicology, University of Zürich, and Swiss Federal Institute of Technology Zürich (ETH), Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
2 Biological Central Laboratory, University Hospital, Sternwartstrasse 6, CH-8091 Zürich, Switzerland.
3 Department Pharma Research Gene Technology, F. Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland.
*   These authors contributed equally to this report.

dagger    Present address: Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

ddagger    To whom correspondence should be addressed. E-mail: rudolph{at}pharma.unizh.ch

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A 2,3 selective agonist, in comparison with lorazepam in healthy volunteers.
S. de Haas, K. Franson, J. Schmitt, A. Cohen, J. Fau, C Dubruc, and J. van Gerven (2009)
J Psychopharmacol 23, 625-632
   Abstract »    PDF »
GABAA Receptor {alpha}5 Subunits Contribute to GABAA,slow Synaptic Inhibition in Mouse Hippocampus.
E. D. Zarnowska, R. Keist, U. Rudolph, and R. A. Pearce (2009)
J Neurophysiol 101, 1179-1191
   Abstract »    Full Text »    PDF »
GABAA Receptors Containing Gamma1 Subunits Contribute to Inhibitory Transmission in the Central Amygdala.
A. Esmaeili, J. W. Lynch, and P. Sah (2009)
J Neurophysiol 101, 341-349
   Abstract »    Full Text »    PDF »
NS11394 [3'-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABAA Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy.
N. R. Mirza, J. S. Larsen, C. Mathiasen, T. A. Jacobsen, G. Munro, H. K. Erichsen, A. N. Nielsen, K. B. Troelsen, E. O. Nielsen, and P. K. Ahring (2008)
J. Pharmacol. Exp. Ther. 327, 954-968
   Abstract »    Full Text »    PDF »
Subunit-Selective Modulation of GABA Type A Receptor Neurotransmission and Cognition in Schizophrenia.
D. A. Lewis, R. Y. Cho, C. S. Carter, K. Eklund, S. Forster, M. A. Kelly, and D. Montrose (2008)
Am J Psychiatry 165, 1585-1593
   Abstract »    Full Text »    PDF »
International Union of Pharmacology. LXX. Subtypes of {gamma}-Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Composition, Pharmacology, and Function. Update.
R. W. Olsen and W. Sieghart (2008)
Pharmacol. Rev. 60, 243-260
   Abstract »    Full Text »    PDF »
The Time-Dependent Effects of Midazolam on Regional Cerebral Glucose Metabolism in Rats.
U. Freo, M. Dam, and C. Ori (2008)
Anesth. Analg. 106, 1516-1523
   Abstract »    Full Text »    PDF »
Metabolism and Disposition of a {gamma}-Aminobutyric Acid Type A Receptor Partial Agonist in Humans.
C. L. Shaffer, M. Gunduz, A. D. Vaz, K. Venkatakrishnan, and A. H. Burstein (2008)
Drug Metab. Dispos. 36, 655-662
   Abstract »    Full Text »    PDF »
Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABAA {alpha}2,3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers.
S.L. de Haas, S.J. de Visser, J.P. van der Post, R.C. Schoemaker, K. van Dyck, M.G. Murphy, M. de Smet, L.K. Vessey, R. Ramakrishnan, L. Xue, et al. (2008)
J Psychopharmacol 22, 24-32
   Abstract »    PDF »
Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome.
L. Medrihan, E. Tantalaki, G. Aramuni, V. Sargsyan, I. Dudanova, M. Missler, and W. Zhang (2008)
J Neurophysiol 99, 112-121
   Abstract »    Full Text »    PDF »
Presynaptic Inhibition of GABAA Receptor-Mediated Unitary IPSPs by Cannabinoid Receptors at Synapses Between CCK-Positive Interneurons in Rat Hippocampus.
A. B. Ali (2007)
J Neurophysiol 98, 861-869
   Abstract »    Full Text »    PDF »
Relative Abuse Liability of Indiplon and Triazolam in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects.
L. P. Carter, R. R. Griffiths, P. E. Suess, J. H. Casada, C. L. Wallace, and J. D. Roache (2007)
J. Pharmacol. Exp. Ther. 322, 749-759
   Abstract »    Full Text »    PDF »
Reduced {gamma}-Aminobutyric AcidA-Benzodiazepine Binding Sites in Insular Cortex of Individuals With Panic Disorder.
O. G. Cameron, G. C. Huang, T. Nichols, R. A. Koeppe, S. Minoshima, D. Rose, and K. A. Frey (2007)
Arch Gen Psychiatry 64, 793-800
   Abstract »    Full Text »    PDF »
Differential contribution of GABAA receptor subtypes to the anticonvulsant efficacy of benzodiazepine site ligands.
R. L. Fradley, M. R. Guscott, S. Bull, D. J. Hallett, S. C. Goodacre, K. A. Wafford, E. M. Garrett, R. J. Newman, G. F. O'Meara, P. J. Whiting, et al. (2007)
J Psychopharmacol 21, 384-391
   Abstract »    PDF »
Pharmacodynamic and pharmacokinetic effects of TPA023, a GABAA {alpha}2,3 subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers.
S.L. de Haas, S.J. de Visser, J.P. van der Post, M. de Smet, R.C. Schoemaker, B. Rijnbeek, A.F. Cohen, J.M. Vega, N.G.B. Agrawal, T.V. Goel, et al. (2007)
J Psychopharmacol 21, 374-383
   Abstract »    PDF »
Giant Spontaneous Depolarizing Potentials in the Developing Thalamic Reticular Nucleus.
S. Pangratz-Fuehrer, U. Rudolph, and J. R. Huguenard (2007)
J Neurophysiol 97, 2364-2372
   Abstract »    Full Text »    PDF »
Effects of Toluene Exposure during Brain Growth Spurt on GABAA Receptor-Mediated Functions in Juvenile Rats.
C.-L. Liu, Y.-R. Lin, M.-H. Chan, and H.-H. Chen (2007)
Toxicol. Sci. 95, 443-451
   Abstract »    Full Text »    PDF »
The Anxioselective Agent 7-(2-Chloropyridin-4-yl)pyrazolo-[1,5-a]-pyrimidin-3-yl](pyridin-2-yl)methanone (DOV 51892) Is More Efficacious Than Diazepam at Enhancing GABA-Gated Currents at {alpha}1 Subunit-Containing GABAA Receptors.
P. Popik, E. Kostakis, M. Krawczyk, G. Nowak, B. Szewczyk, P. Krieter, Z. Chen, S. J. Russek, T. T. Gibbs, D. H. Farb, et al. (2006)
J. Pharmacol. Exp. Ther. 319, 1244-1252
   Abstract »    Full Text »    PDF »
{gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment..
J. H. Krystal, J. Staley, G. Mason, I. L. Petrakis, J. Kaufman, R. A. Harris, J. Gelernter, and J. Lappalainen (2006)
Arch Gen Psychiatry 63, 957-968
   Abstract »    Full Text »    PDF »
Specific Subtypes of GABAA Receptors Mediate Phasic and Tonic Forms of Inhibition in Hippocampal Pyramidal Neurons.
G. A. Prenosil, E. M. Schneider Gasser, U. Rudolph, R. Keist, J.-M. Fritschy, and K. E. Vogt (2006)
J Neurophysiol 96, 846-857
   Abstract »    Full Text »    PDF »
RAT PHARMACOKINETICS AND PHARMACODYNAMICS OF A SUSTAINED RELEASE FORMULATION OF THE GABAA {alpha}5-SELECTIVE COMPOUND L-655,708.
J. R. Atack, A. Pike, A. Clarke, S. M. Cook, B. Sohal, R. M. McKernan, and G. R. Dawson (2006)
Drug Metab. Dispos. 34, 887-893
   Abstract »    Full Text »    PDF »
Intrinsic and synaptic dynamics interact to generate emergent patterns of rhythmic bursting in thalamocortical neurons..
V. S. Sohal, S. Pangratz-Fuehrer, U. Rudolph, and J. R. Huguenard (2006)
J. Neurosci. 26, 4247-4255
   Abstract »    Full Text »    PDF »
Fast IPSCs in rat thalamic reticular nucleus require the GABAA receptor {beta}1 subunit.
M. M. Huntsman and J. R. Huguenard (2006)
J. Physiol. 572, 459-475
   Abstract »    Full Text »    PDF »
Indiplon Is a High-Affinity Positive Allosteric Modulator with Selectivity for {alpha}1 Subunit-Containing GABAA Receptors.
R. E. Petroski, J. E. Pomeroy, R. Das, H. Bowman, W. Yang, A. P. Chen, and A. C. Foster (2006)
J. Pharmacol. Exp. Ther. 317, 369-377
   Abstract »    Full Text »    PDF »
Comparative Cue Generalization Profiles of L-838, 417, SL651498, Zolpidem, CL218,872, Ocinaplon, Bretazenil, Zopiclone, and Various Benzodiazepines in Chlordiazepoxide and Zolpidem Drug Discrimination.
N. R. Mirza, R. J. Rodgers, and L. S. Mathiasen (2006)
J. Pharmacol. Exp. Ther. 316, 1291-1299
   Abstract »    Full Text »    PDF »
Do Subtype-Selective {gamma}-Aminobutyric AcidA Receptor Modulators Have a Reduced Propensity to Induce Physical Dependence in Mice?.
N. R. Mirza and E. O. Nielsen (2006)
J. Pharmacol. Exp. Ther. 316, 1378-1385
   Abstract »    Full Text »    PDF »
TPA023 [7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an Agonist Selective for {alpha}2- and {alpha}3-Containing GABAA Receptors, Is a Nonsedating Anxiolytic in Rodents and Primates.
J. R. Atack, K. A. Wafford, S. J. Tye, S. M. Cook, B. Sohal, A. Pike, C. Sur, D. Melillo, L. Bristow, F. Bromidge, et al. (2006)
J. Pharmacol. Exp. Ther. 316, 410-422
   Abstract »    Full Text »    PDF »
A schizophrenia-related sensorimotor deficit links {alpha}3-containing GABAA receptors to a dopamine hyperfunction.
B. K. Yee, R. Keist, L. von Boehmer, R. Studer, D. Benke, N. Hagenbuch, Y. Dong, R. C. Malenka, J.-M. Fritschy, H. Bluethmann, et al. (2005)
PNAS 102, 17154-17159
   Abstract »    Full Text »    PDF »
Evidence for a Significant Role of {alpha}3-Containing GABAA Receptors in Mediating the Anxiolytic Effects of Benzodiazepines.
R. Dias, W. F. A. Sheppard, R. L. Fradley, E. M. Garrett, J. L. Stanley, S. J. Tye, S. Goodacre, R. J. Lincoln, S. M. Cook, R. Conley, et al. (2005)
J. Neurosci. 25, 10682-10688
   Abstract »    Full Text »    PDF »
Characterization in Rats of the Anxiolytic Potential of ELB139 [1-(4-Chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-on], a New Agonist at the Benzodiazepine Binding Site of the GABAA Receptor.
B. Langen, U. Egerland, K. Bernoster, R. Dost, K. Unverferth, and C. Rundfeldt (2005)
J. Pharmacol. Exp. Ther. 314, 717-724
   Abstract »    Full Text »    PDF »
{alpha}1 Subunit-Containing GABA Type A Receptors in Forebrain Contribute to the Effect of Inhaled Anesthetics on Conditioned Fear.
J. M. Sonner, M. Cascio, Y. Xing, M. S. Fanselow, J. E. Kralic, A. L. Morrow, E. R. Korpi, S. Hardy, B. Sloat, E. I. Eger II, et al. (2005)
Mol. Pharmacol. 68, 61-68
   Abstract »    Full Text »    PDF »
Contribution of GABAA Receptor Subtypes to the Anxiolytic-Like, Motor, and Discriminative Stimulus Effects of Benzodiazepines: Studies with the Functionally Selective Ligand SL651498 [6-Fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyridol[3,4-b]indol-1-one].
S. C. Licata, D. M. Platt, J. M. Cook, P. V. V. S. Sarma, G. Griebel, and J. K. Rowlett (2005)
J. Pharmacol. Exp. Ther. 313, 1118-1125
   Abstract »    Full Text »    PDF »
Selective anxiolysis produced by ocinaplon, a GABAA receptor modulator.
A. Lippa, P. Czobor, J. Stark, B. Beer, E. Kostakis, M. Gravielle, S. Bandyopadhyay, S. J. Russek, T. T. Gibbs, D. H. Farb, et al. (2005)
PNAS 102, 7380-7385
   Abstract »    Full Text »    PDF »
Making sense of GABAA receptor subtypes: is a new nomenclature needed?.
D. J. Nutt (2005)
J Psychopharmacol 19, 219-220
   PDF »
Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates.
J. K. Rowlett, D. M. Platt, S. Lelas, J. R. Atack, and G. R. Dawson (2005)
PNAS 102, 915-920
   Abstract »    Full Text »    PDF »
In Vivo Pharmacological Characterization of Indiplon, a Novel Pyrazolopyrimidine Sedative-Hypnotic.
A. C. Foster, M. A. Pelleymounter, M. J. Cullen, D. Lewis, M. Joppa, T. K. Chen, H. P. Bozigian, R. S. Gross, and K. R. Gogas (2004)
J. Pharmacol. Exp. Ther. 311, 547-559
   Abstract »    Full Text »    PDF »
Characterization of the Interaction of Indiplon, a Novel Pyrazolopyrimidine Sedative-Hypnotic, with the GABAA Receptor.
S. K. Sullivan, R. E. Petroski, G. Verge, R. S. Gross, A. C. Foster, and D. E. Grigoriadis (2004)
J. Pharmacol. Exp. Ther. 311, 537-546
   Abstract »    Full Text »    PDF »
Analysis of the Presence and Abundance of GABAA Receptors Containing Two Different Types of {alpha} Subunits in Murine Brain Using Point-mutated {alpha} Subunits.
D. Benke, P. Fakitsas, C. Roggenmoser, C. Michel, U. Rudolph, and H. Mohler (2004)
J. Biol. Chem. 279, 43654-43660
   Abstract »    Full Text »    PDF »
Requirement of {alpha}5-GABAA Receptors for the Development of Tolerance to the Sedative Action of Diazepam in Mice.
C. van Rijnsoever, M. Tauber, M. K. Choulli, R. Keist, U. Rudolph, H. Mohler, J. M. Fritschy, and F. Crestani (2004)
J. Neurosci. 24, 6785-6790
   Abstract »    Full Text »    PDF »
Variability in the Benzodiazepine Response of Serotonin 5-HT1A Receptor Null Mice Displaying Anxiety-Like Phenotype: Evidence for Genetic Modifiers in the 5-HT-Mediated Regulation of GABAA Receptors.
S. J. Bailey and M. Toth (2004)
J. Neurosci. 24, 6343-6351
   Abstract »    Full Text »    PDF »
Specific GABAA Circuits for Visual Cortical Plasticity.
M. Fagiolini, J.-M. Fritschy, K. Low, H. Mohler, U. Rudolph, and T. K. Hensch (2004)
Science 303, 1681-1683
   Abstract »    Full Text »    PDF »
Modulation of rhythmic brain activity by diazepam: GABAAreceptor subtype and state specificity.
C. Kopp, U. Rudolph, K. Low, and I. Tobler (2004)
PNAS 101, 3674-3679
   Abstract »    Full Text »    PDF »
Neurosteroids Shift Partial Agonist Activation of GABAA Receptor Channels from Low- to High-Efficacy Gating Patterns.
M. T. Bianchi and R. L. Macdonald (2003)
J. Neurosci. 23, 10934-10943
   Abstract »    Full Text »    PDF »
Repeated neonatal handling with maternal separation permanently alters hippocampal GABAA receptors and behavioral stress responses.
F.-C. Hsu, G.-J. Zhang, Y. S. H. Raol, R. J. Valentino, D. A. Coulter, and A. R. Brooks-Kayal (2003)
PNAS 100, 12213-12218
   Abstract »    Full Text »    PDF »
Glycine Receptor Knock-In Mice and Hyperekplexia-Like Phenotypes: Comparisons with the Null Mutant.
G. S. Findlay, R. Phelan, M. T. Roberts, G. E. Homanics, S. E. Bergeson, G. F. Lopreato, S. J. Mihic, Y. A. Blednov, and R. A. Harris (2003)
J. Neurosci. 23, 8051-8059
   Abstract »    Full Text »    PDF »
Dynamic GABAA Receptor Subtype-Specific Modulation of the Synchrony and Duration of Thalamic Oscillations.
V. S. Sohal, R. Keist, U. Rudolph, and J. R. Huguenard (2003)
J. Neurosci. 23, 3649-3657
   Abstract »    Full Text »    PDF »
Anxiogenic Effects of Neurosteroid Exposure: Sex Differences and Altered GABAA Receptor Pharmacology in Adult Rats.
M. Gulinello and S. S. Smith (2003)
J. Pharmacol. Exp. Ther. 305, 541-548
   Abstract »    Full Text »    PDF »
gamma -Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABAA Receptors alpha 4 Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells.
P. Follesa, L. Mancuso, F. Biggio, M. C. Mostallino, A. Manca, M. P. Mascia, F. Busonero, G. Talani, E. Sanna, and G. Biggio (2003)
Mol. Pharmacol. 63, 896-907
   Abstract »    Full Text »    PDF »
Withdrawal from Chronic Intermittent Ethanol Treatment Changes Subunit Composition, Reduces Synaptic Function, and Decreases Behavioral Responses to Positive Allosteric Modulators of GABAA Receptors.
E. Cagetti, J. Liang, I. Spigelman, and R. W. Olsen (2003)
Mol. Pharmacol. 63, 53-64
   Abstract »    Full Text »    PDF »
Disruption of Coherent Oscillations in Inhibitory Networks With Anesthetics: Role of GABAA Receptor Desensitization.
P. M. Baker, P. S. Pennefather, B. A. Orser, and F. K. Skinner (2002)
J Neurophysiol 88, 2821-2833
   Abstract »    Full Text »    PDF »
5-Ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N- (2-fluorophenyl)carboxamide (RWJ-51204), a New Nonbenzodiazepine Anxiolytic.
B. Dubinsky, A. H. Vaidya, D. I. Rosenthal, C. Hochman, J. J. Crooke, S. DeLuca, A. DeVine, C. T. Cheo-Isaacs, A. R. Carter, A. D. Jordan, et al. (2002)
J. Pharmacol. Exp. Ther. 303, 777-790
   Abstract »    Full Text »    PDF »
Molecular and Pharmacological Characterization of GABAA Receptor alpha 1 Subunit Knockout Mice.
J. E. Kralic, E. R. Korpi, T. K. O'Buckley, G. E. Homanics, and A. L. Morrow (2002)
J. Pharmacol. Exp. Ther. 302, 1037-1045
   Abstract »    Full Text »    PDF »
Molecular Actions of (S)-Desmethylzopiclone (SEP-174559), an Anxiolytic Metabolite of Zopiclone.
M. W. Fleck (2002)
J. Pharmacol. Exp. Ther. 302, 612-618
   Abstract »    Full Text »    PDF »
Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the alpha 5 Subunit of the GABAA Receptor.
N. Collinson, F. M. Kuenzi, W. Jarolimek, K. A. Maubach, R. Cothliff, C. Sur, A. Smith, F. M. Otu, O. Howell, J. R. Atack, et al. (2002)
J. Neurosci. 22, 5572-5580
   Abstract »    Full Text »    PDF »
Trace fear conditioning involves hippocampal alpha 5 GABAA receptors.
F. Crestani, R. Keist, J.-M. Fritschy, D. Benke, K. Vogt, L. Prut, H. Bluthmann, H. Mohler, and U. Rudolph (2002)
PNAS 99, 8980-8985
   Abstract »    Full Text »    PDF »
Transgenic Expression of a Mutant Glycine Receptor Decreases Alcohol Sensitivity of Mice.
G. S. Findlay, M. J. Wick, M. P. Mascia, D. Wallace, G. W. Miller, R. A. Harris, and Y. A. Blednov (2002)
J. Pharmacol. Exp. Ther. 300, 526-534
   Abstract »    Full Text »    PDF »
A New Benzodiazepine Pharmacology.
H. Mohler, J. M. Fritschy, and U. Rudolph (2002)
J. Pharmacol. Exp. Ther. 300, 2-8
   Abstract »    Full Text »    PDF »
New insights into the role of the GABAA--benzodiazepine receptor in psychiatric disorder.
D. J. NUTT and A. L. MALIZIA (2001)
The British Journal of Psychiatry 179, 390-396
   Abstract »    Full Text »    PDF »
A GABAB Mystery: The Search for Pharmacologically Distinct GABAB Receptors.
S. J. Enna (2001)
Mol. Interv. 1, 208-218
   Abstract »    Full Text »    PDF »
SL651498: An Anxioselective Compound with Functional Selectivity for alpha 2- and alpha 3-Containing gamma -Aminobutyric AcidA (GABAA) Receptors.
G. Griebel, G. Perrault, J. Simiand, C. Cohen, P. Granger, M. Decobert, D. Francon, P. Avenet, H. Depoortere, S. Tan, et al. (2001)
J. Pharmacol. Exp. Ther. 298, 753-768
   Abstract »    Full Text »    PDF »
Anxiety at the Frontier of Molecular Medicine.
D. R. Weinberger (2001)
N. Engl. J. Med. 344, 1247-1249
   Full Text »    PDF »
Perspectives on Neuroscience and Behavior.
(2001)
Neuroscientist 7, 91-92
   PDF »
Zolpidem, Triazolam, and Diazepam Decrease Distress Vocalizations in Mouse Pups: Differential Antagonism by Flumazenil and {beta}-Carboline-3-carboxylate-t-butyl ester ({beta}-CCt).
J. K. Rowlett, W. Tornatzky, J. M. Cook, C. Ma, and K. A. Miczek (2001)
J. Pharmacol. Exp. Ther. 297, 247-253
   Abstract »    Full Text »
Glutamic acid decarboxylase and glutamate receptor changes during tolerance and dependence to benzodiazepines.
E. Izzo, J. Auta, F. Impagnatiello, C. Pesold, A. Guidotti, and E. Costa (2001)
PNAS 98, 3483-3488
   Abstract »    Full Text »    PDF »
Molecular Targets for the Myorelaxant Action of Diazepam.
F. Crestani, K. Löw, R. Keist, M.-J. Mandelli, H. Möhler, and U. Rudolph (2001)
Mol. Pharmacol. 59, 442-445
   Abstract »    Full Text »
Anxiety-Reducing Benzodiazepine Receptor Identified.
(2000)
Journal Watch (General) 2000, 7
   Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)