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Title Neurosteroid effects in the central nervous system : the role of the GABA-A receptor / edited by Sheryl S. Smith
Published Boca Raton : CRC Press, 2003
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Description 1 online resource (408 pages)
Series Methods & new frontiers in neuroscience
Methods & new frontiers in neuroscience series.
Contents Front cover -- Series Preface -- Editor -- Contributors -- Contents -- Introduction -- GABA-Modulatory Steroids -- 3a,5a-THP: Historical Overview of Physiological Effect -- The GABAA Receptor -- References -- Commonly Used Steroid Abbreviations in the Book -- Contents -- 1 -- Synthesis, Enzyme Localization, and Regulation of Neurosteroids -- Abstract -- 1.1 Neurosteroids -- 1.2 Enzymes Involved in Neurosteroidogenesis: Biochemistry and Molecular Biology -- 1.2.1 Cytochrome P450 -- 1.2.2 Hydroxysteroid Dehydrogenases -- 1.2.3 Neurosteroidogenic Enzymes: P450s -- 1.2.3.1 P450scc:Cholesterol Æ Pregnenolone -- 1.2.3.2 Transport of Electrons to P450scc: Adrenodoxin Reductase and Adrenodoxin -- 1.2.3.3 StAR -- 1.2.3.4 3b HSD: Pregnenolone Æ Progesterone 17-OH-Pregnenolone Æ 17-OH-Progesterone DHEA Æ Androstenedione -- 1.2.3.5 P450c17: Pregnenolone Æ 17-OH-Pregnenolone Æ DHEA Progesterone Æ 17-OH-Progesterone Æ Androstenedione -- 1.2.3.6 P450c21: Progesterone Æ 11-Deoxycorticosterone 17-OH- Progesterone Æ 11-Deoxycortisol -- 1.2.3.7 P450 Reductase -- 1.2.3.8 Cytochrome b5 -- 1.2.3.9 P450c11: 11-Deoxycortisocterone Æ Corticosterone Corticosterone Æ 18-OH-Corticosterone Æ Aldosterone -- 1.2.3.10 P450aro:Testosterone Æ Estradiol -- 1.2.4 Neurosteroidogenic Enzymes: Non-P450s -- 1.2.4.1 17b HSD: DHEA ́Androstenediol Androstenedione ́Testosterone Estrone ́Estradiol -- 1.2.4.2 11b HSD: Cortisol ́Cortisone -- 1.2.4.3 5a-Reductase: Progesterone Æ 5a-Dihydroprogesterone 11-Deoxycorticosterone Æ 5a-11-Deoxycorticosterone Testosterone Æ DHT -- 1.2.4.4 3a HSD/3a-Hydroxysteroid Oxidoreductase: 5a-Dihydroprogesterone ́3a5a-Tetrahydroprogesterone (Allopregnanolone) 5a DOC ́3a5a-TetrahydroDOC DHT ́Androstanediol -- 1.2.4.5 Sulfotransferase (HST) -- 1.2.4.6 Sulfatase (STS) -- 1.2.4.7 Other Neurosteroidogenic Enzymes
1.3 Enzymes Involved in Neurosteroidogenesis: Distribution in the Brain -- 1.3.1 Expression of P450scc in the Adult Rat Brain -- 1.3.2 Expression of Adrenodoxin and Adrenodoxin Reductase in the Brain -- 1.3.3 Expression of StAR in the Brain -- 1.3.4 P450c17 Expression in the Nervous System -- 1.3.5 Expression and Activity of P450 Reductase and b5 in the Brain -- 1.3.6 3b HSD Expression in the Adult Nervous System -- 1.3.7 P450c11: P450c11b and P450c11AS Expression in the Adult Nervous System -- 1.3.8 Expression of 17b HSD in the Brain -- 1.3.9 Expression of P450aro in the Brain -- 1.3.10 Expression of 11b HSD in the Brain -- 1.3.11 Expression of 5a-Reductase in the Brain -- 1.3.12 Expression of 3a HSD in the Brain -- 1.3.13 Expression of HST in the Brain -- 1.3.14 Activity and Expression of STS in the Brain -- 1.4 Regulation of Neurosteroidogenic Enzymes -- 1.4.1 Regulation of 3a HSD -- 1.4.2 Inhibition of 3a HSD by Benzodiazepines -- 1.4.3 Regulation of 3bHSD by GABA -- 1.4.4 Regulation of Allopregnanolone Production by Ethanol -- References -- 2 -- Subunit Specificity of Steroid Modulation of GABAA Receptors -- 2.1 Introduction -- 2.1.1 GABAA Receptors -- 2.1.2 Neuroactive Steroids and GABAR -- 2.2 Heterogeneity in Steroid-GABAR Interactions in Animals, Cells, Sections/Slices, or Homogenates -- 2.2.1 Radioligand Binding Studies -- 2.2.1.1 Observations -- 2.2.1.2 Possible Interpretations -- 2.2.2 Pharmacology -- 2.2.2.1 Regional and Age Differences Detected by Electrophysiology -- 2.2.2.2 Sex Differences -- 2.2.2.3 Plasticity -- 2.2.2.4 The GABAR d Subunit Knockout Mouse -- 2.2.2.5 Possible Non-GABAR Mechanisms for Differential Sensitivity to Neuroactive Steroids -- 2.3 Recombinant Receptor Studies
2.3.1 Subunit Composition Provides Partial Explanation for Heterogeneity in Concentration Dependence of Neuroactive Steroid Modulation of GABAR Binding -- 2.3.2 Subunit Selectivity for Neuroactive Steroid Modulation of Recombinant GABAR Subunits Expressed in Heterologous Cells -- 2.3.2.1 Subunit Selectivity Involving a -- 2.3.2.2 Subunit Selectivity Involving b -- 2.3.2.3 Subunit Selectivity Involving g -- 2.3.2.4 Subunit Selectivity Involving d -- 2.3.2.5 Subunit Selectivity Involving e -- 2.3.2.6 Subunit Selectivity Involving r -- References -- 3 -- THDOC and the GABAA Receptor -- 3.1 Historical Notes on the Effects of Steroidal Drugs on GABAergic Synaptic Transmission: The Prolongation of Decay as Major Effects of Steroids -- 3.2 The Isolation of Endogenous Steroids and Minimal Structural Requirement for THDOC Action -- 3.3 The Discovery of the Key Role of Desensitization in GABA Channel Deactivation and the Action of THDOC and Other Modulators -- 3.4 Evidence for Heterogeneity of THDOC Action in Native GABA Receptors -- References -- 4 -- Neurosteroid Modulation of d Subunit- Containing GABAA Receptor Channels -- 4.1 Introduction -- 4.2 d Subunit Expression and Receptor Assembly -- 4.3 Tonic and Phasic Inhibition -- 4.4 Functional Properties of d Subunit- Containing Receptors -- 4.5 Effects of Neurosteroids on abd Receptor Currents -- 4.6 Insights from d-Subunit Knockout Mice -- 4.7 Role of Phosphorylation and Co-Modulation -- 4.8 Conclusions -- References -- 5 -- Potentiation and Inhibition of GABAA Receptor Function by Neuroactive Steroids -- 5.1 Introduction -- 5.2 Endogenous GABA-Potentiating and GABA-Inhibiting Steroids -- 5.3 Non-GABAA Receptor Targets of Neuroactive Steroids -- 5.3.1 Glycine Receptors -- 5.3.2 Ionotropic Glutamate Receptors -- 5.3.3 Nicotinic Acetylcholine Receptors -- 5.3.4 5-HT3 Serotonin Receptors
5.3.5 Voltage-Gated Ca2+ Channels -- 5.3.6 s1 Receptors -- 5.3.7 Summary of Other Targets -- 5.4 Clinical Relevance of GABA-Active Steroids -- 5.4.1 GABA-Potentiating Steroids -- 5.4.2 GABA-Inhibiting Steroids -- 5.4.3 Summary of Clinical Relevance of Neuroactive Steroids -- 5.5 Studies of Structure-Activity Relationships -- 5.5.1 GABA-Potentiating Steroids -- 5.5.2 GABA-Inhibiting Steroids -- 5.5.3 Summary of Structure-Activity Studies -- 5.6 Mechanism and Synaptic Effects of GABA-Inhibiting Steroids -- 5.6.1 Summary of Mechanisms and Synaptic Effects of GABA-Inhibiting Steroids -- 5.7 Conclusions -- References -- 6 -- Anabolic Androgenic Steroids and the Brain: Novel Actions at the GABAA Receptor and on GABAA Receptor- Mediated Behaviors -- 6.1 History of AAS Development -- 6.1.1 Therapeutic Use of AASs -- 6.1.2 Abuse of AASs -- 6.1.3 Characterization of AAS Chemistry -- 6.2 AAS Modulation of GABAA Receptor Function and Expression -- 6.2.1 Allosteric Modulation of GABAA Receptors -- 6.2.1.1 GABAA Receptor Subunit Complexity -- 6.2.1.2 AASs Induce Allosteric Modulation of GABAA Receptors -- 6.2.1.3 AAS- vs. Neurosteroid-Induced Allosteric Modulation -- 6.2.1.4 AAS- vs. Benzodiazepine-Induced Allosteric Modulation -- 6.2.1.5 Kinetic Modeling of AAS Allosteric Modulation -- 6.2.1.6 Subunit Specificity of AAS Allosteric Modulation -- 6.2.2 Regulation of GABAA Receptor Expression by Chronic AAS Treatment -- 6.3 Behavioral Correlates of AAS Administration on Behaviors Mediated by GABAergic Transmission -- 6.3.1 Anxiety -- 6.3.2 Aggression -- 6.3.3 Female Sexual Behavior -- 6.4 Summary -- References -- 7 -- Withdrawal Effects of a Neuroactive Steroid as a Model of PMS: Synaptic Physiology to Behavior -- Abbreviations -- 7.1 Introduction -- 7.2 Steroid Withdrawal and Behavioral Excitability -- 7.3 Steroid Withdrawal and GABAR Pharmacology
7.4 Steroid Withdrawal: Other Brain Regions and GABA Modulators -- 7.5 Cross-Tolerance with Other GABA Modulators -- 7.6 Steroid Withdrawal: Hypothalamic Neurons -- 7.7 Chronic Neurosteroid Exposure -- 7.8 Time Course of Steroid-Induced Changes in a4 Subunit Expression -- 7.9 Pharmacology of Behavioral Changes Associated with Chronic steroid Exposure and Withdrawal -- 7.10 a4 Subunit Expression and Inhibitory Tone -- 7.11 A Model of Hippocampal Excitability: Paired Pulse Inhibition -- 7.12 PPI in CA1 Hippocampus: Circuit Properties -- 7.13 Recurrent Inhibition and PPI -- 7.14 PPI and Neuronal Excitability -- 7.15 Alterations in Synaptic Current after 48-h 3a,5b-THP Treatment -- 7.16 Current Deactivation -- 7.17 The GABAR d Subunit -- 7.18 Ethanol Effects on a4bd GABAR -- 7.19 Extrasynaptic GABAR -- 7.20 Neurosteroid Effects on Extrasynaptic GABAR -- 7.21 Conclusions -- Acknowledgments -- References -- 8 -- GABA, Estrogen, and Sex Differences in the Brain -- 8.1 Introduction -- 8.2 Sexual Differentiation of the Brain -- 8.3 g-Aminobutyric Acid (GABA) -- 8.3.1 Sex Differences in the GABA System during the Perinatal Sensitive Period -- 8.3.2 GABA Is Excitatory in the Developing Brain -- 8.3.3 GABA as Both a Neurotrophic and Neurotoxic Agent during Development -- 8.3.4 Estradiol Enhances Excitatory GABA -- 8.3.5 GABAA Receptor Activation Increases Phosphorylation of CREB in Males but Decreases It in Females -- 8.3.6 GABAA Receptor Activation Mediates Sexually Dimorphic Astrocyte Morphology -- 8.4 Summary and Future Perspectives -- References -- 9 -- FGIN-1-X: A Series of Novel Specific and Efficacious Ligands for the Peripheral Benzodiazepine Receptor -- Abstract -- 9.1 Introduction -- 9.2 Pharmacology and Structure-Activity Studies of FGIN-1 Compounds -- 9.3 Localization and Function of the Peripheral Benzodiazepine Receptor
Bibliography Includes bibliographical references and index
Subject Receptors, GABA-A -- physiology.
Central Nervous System -- physiology.
GABA -- Receptors.
Neurohormones -- Physiological effect
Neurotransmitter receptors.
Steroids -- Physiological effect
GABA -- Receptors.
Neurotransmitter receptors.
Steroids -- Physiological effect.
Form Electronic book
Author Smith, Sheryl S.
ISBN 0203508165
9780203508169