{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T22:33:50Z","timestamp":1776724430697,"version":"3.51.2"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Network communication in the CNS relies upon multiple neuronal and glial signaling pathways. In addition to synaptic transmission, other organelles such as mitochondria play roles in cellular signaling. One highly conserved mitochondrial signaling mechanism involves the 18\u00a0kDa translocator protein (TSPO) of the outer mitochondrial membrane. Originally, TSPO was identified as a binding site for benzodiazepines in the periphery. It was later discovered that TSPO is found in mitochondria, including in CNS cells. TSPO is implicated in multiple cellular processes, including the translocation of cholesterol and steroidogenesis, porphyrin transport, cellular responses to stress, inflammation, and tumor progression. Yet the impacts of modulating TSPO signaling on network activity and behavioral performance have not been characterized. In the present study, we assessed the effects of TSPO modulators PK11195, Ro5-4864, and XBD-173 via electroencephalography (EEG) and the open field test (OFT) at low to moderate doses. Cortical EEG recordings revealed increased power in the \u03b4 and \u03b8 frequency bands after administration of each of the three modulators, as well as compound- and dose-specific changes in \u03b1 and \u03b3. Behaviorally, these compounds reduced locomotor activity in the OFT in a dose-dependent manner, with XBD-173 having the subtlest behavioral effects while still strongly modulating the EEG. These findings indicate that TSPO modulators, despite their diversity, exert similar effects on the EEG while displaying a range of sedative\/hypnotic effects at moderate to high doses. These findings bring us one step closer to understanding the functions of TSPO in the brain and as a target in CNS disease.<\/jats:p>","DOI":"10.3389\/fphar.2022.750554","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T08:35:40Z","timestamp":1649061340000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative Assessment of TSPO Modulators on Electroencephalogram Activity and Exploratory Behavior"],"prefix":"10.3389","volume":"13","author":[{"given":"Rochelle M.","family":"Hines","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine A.","family":"Aquino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew I.","family":"Khumnark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria P.","family":"D\u00e1vila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin J.","family":"Hines","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/sj.npp.1380110","article-title":"Dynamics of Slow-Wave Activity and Spindle Frequency Activity in the Human Sleep EEG: Effect of Midazolam and Zopiclone","volume":"11","author":"Aeschbach","year":"1994","journal-title":"Neuropsychopharmacology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1007\/s12035-020-02136-5","article-title":"Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons","volume":"58","author":"Barron","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.tibs.2015.07.001","article-title":"Enigmatic Translocator Protein (TSPO) and Cellular Stress Regulation","volume":"40","author":"Batoko","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s41181-019-0058-3","article-title":"Molecular Imaging of Multiple Sclerosis: from the Clinical Demand to Novel Radiotracers","volume":"4","author":"Bauckneht","year":"2019","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1016\/0024-3205(84)90048-1","article-title":"Opposite Effects of an Agonist, RO5-4864, and an Antagonist, PK 11195, of the Peripheral Type Benzodiazepine Binding Sites on Audiogenic Seizures in DBA\/2J Mice","volume":"34","author":"B\u00e9navid\u00e8s","year":"1984","journal-title":"Life Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"E512","DOI":"10.3390\/cells9020512","article-title":"The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes","volume":"9","author":"Betlazar","year":"2020","journal-title":"Cells"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3104","DOI":"10.1073\/pnas.1416900112","article-title":"Oxytocin Prevents Ethanol Actions at \u03b4 Subunit-Containing GABAA Receptors and Attenuates Ethanol-Induced Motor Impairment in Rats","volume":"112","author":"Bowen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3805","DOI":"10.1073\/pnas.74.9.3805","article-title":"Specific Benzodiazepine Receptors in Rat Brain Characterized by High-Affinity (3H)diazepam Binding","volume":"74","author":"Braestrup","year":"1977","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"574","DOI":"10.2174\/18715273113126660194","article-title":"Concentration-dependent Bimodal Effect of Specific 18 kDa Translocator Protein (TSPO) Ligands on Cell Death Processes Induced by Ammonium Chloride: Potential Implications for Neuropathological Effects Due to Hyperammonemia","volume":"13","author":"Caballero","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"B10","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1161\/01.cir.73.3.476","article-title":"Peripheral-type Benzodiazepine Receptors in the Living Heart Characterized by Positron Emission Tomography","volume":"73","author":"Charbonneau","year":"1986","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1210\/en.2012-2226","article-title":"Drug Ligand-Induced Activation of Translocator Protein (TSPO) Stimulates Steroid Production by Aged Brown Norway Rat Leydig Cells","volume":"154","author":"Chung","year":"2013","journal-title":"Endocrinology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1365-2990.2008.01006.x","article-title":"Expression of the Translocator Protein of 18 kDa by Microglia, Macrophages and Astrocytes Based on Immunohistochemical Localization in Abnormal Human Brain","volume":"35","author":"Cosenza-Nashat","year":"2009","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"18164","DOI":"10.1038\/srep18164","article-title":"TSPO Ligand Residence Time: a New Parameter to Predict Compound Neurosteroidogenic Efficacy","volume":"6","author":"Costa","year":"2016","journal-title":"Sci. Rep."},{"key":"B14","first-page":"954","article-title":"Sedation after Cardiac Arrest and during Therapeutic Hypothermia","volume":"80","author":"Dell'Anna","year":"2014","journal-title":"Minerva Anestesiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"E870","DOI":"10.3390\/cells9040870","article-title":"Diagnostic and Therapeutic Potential of TSPO Studies Regarding Neurodegenerative Diseases, Psychiatric Disorders, Alcohol Use Disorders, Traumatic Brain Injury, and Stroke: An Update","volume":"9","author":"Dimitrova-Shumkovska","year":"2020","journal-title":"Cells"},{"key":"B16","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/fnagi.2017.00208","article-title":"Microglial Activation in Traumatic Brain Injury","volume":"9","author":"Donat","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1159\/000442210","article-title":"Pharmaco-EEG Studies in Animals: An Overview of Contemporary Translational Applications","volume":"72","author":"Drinkenburg","year":"2015","journal-title":"Neuropsychobiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/BF00427773","article-title":"On the Convulsant Action of Ro 5-4864 and the Existence of a Micromolar Benzodiazepine Binding Site in Rat Brain","volume":"82","author":"File","year":"1984","journal-title":"Psychopharmacology (Berl)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/0304-3940(83)90532-3","article-title":"The Anxiogenic Action of Ro 5-4864 Is Reversed by Phenytoin","volume":"35","author":"File","year":"1983","journal-title":"Neurosci. Lett."},{"key":"B20","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1007\/BF00427962","article-title":"RO5-4864, a Ligand for Benzodiazepine Micromolar and Peripheral Binding Sites: Antagonism and Enhancement of Behavioural Effects","volume":"80","author":"File","year":"1983","journal-title":"Psychopharmacology (Berl)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1111\/j.1476-5381.1984.tb16509.x","article-title":"Pro- and Anti-convulsant Properties of PK 11195, a Ligand for Benzodiazepine Binding Sites: Development of Tolerance","volume":"83","author":"File","year":"1984","journal-title":"Br. J. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"637171","DOI":"10.1155\/2012\/637171","article-title":"Sedation in Traumatic Brain Injury","volume":"2012","author":"Flower","year":"2012","journal-title":"Emerg. Med. Int."},{"key":"B23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/s0014-2999(03)01789-8","article-title":"Antidepressant-like Effect of Ro5-4864, a Peripheral-type Benzodiazepine Receptor Ligand, in Forced Swimming Test","volume":"471","author":"Gavioli","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3752","DOI":"10.1523\/JNEUROSCI.2070-18.2019","article-title":"Translocator Protein Ligand Protects against Neurodegeneration in the MPTP Mouse Model of Parkinsonism","volume":"39","author":"Gong","year":"2019","journal-title":"J. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.3390\/cells10102784","article-title":"Neurogenic Potential of the 18-kDa Mitochondrial Translocator Protein (TSPO) in Pluripotent P19 Stem Cells","volume":"10","author":"Gonz\u00e1lez-Blanco","year":"2021","journal-title":"Cells"},{"key":"B26","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0149-7634(95)00055-0","article-title":"The Transition from Slow-Wave Sleep to Paradoxical Sleep: Evolving Facts and Concepts of the Neurophysiological Processes Underlying the Intermediate Stage of Sleep","volume":"20","author":"Gottesmann","year":"1996","journal-title":"Neurosci. Biobehav Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"706894","DOI":"10.3389\/fphar.2021.706894","article-title":"Mice Lacking GABAA Receptor \u03b4 Subunit Have Altered Pharmaco-EEG Responses to Multiple Drugs","volume":"12","author":"Grotell","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.neuroimage.2011.02.020","article-title":"Age and Disease Related Changes in the Translocator Protein (TSPO) System in the Human Brain: Positron Emission Tomography Measurements with [11C]vinpocetine","volume":"56","author":"Guly\u00e1s","year":"2011","journal-title":"NeuroImage"},{"key":"B29","first-page":"831","article-title":"Peripheral-type Benzodiazepine Receptor (PBR) in Human Breast Cancer: Correlation of Breast Cancer Cell Aggressive Phenotype with PBR Expression, Nuclear Localization, and PBR-Mediated Cell Proliferation and Nuclear Transport of Cholesterol","volume":"59","author":"Hardwick","year":"1999","journal-title":"Cancer Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1126\/science.1248725","article-title":"Structure of the Mitochondrial Translocator Protein in Complex with a Diagnostic Ligand","volume":"343","author":"Jaremko","year":"2014","journal-title":"Science"},{"key":"B31","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1042\/BST20150029","article-title":"Structure of the Mammalian TSPO\/PBR Protein","volume":"43","author":"Jaremko","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"B32","doi-asserted-by":"publisher","first-page":"12255","DOI":"10.1523\/JNEUROSCI.2312-08.2008","article-title":"Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies","volume":"28","author":"Ji","year":"2008","journal-title":"J. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1080\/13543776.2016.1230606","article-title":"Translocator Protein (TSPO) Ligands for the Diagnosis or Treatment of Neurodegenerative Diseases: a Patent Review (2010-2015; Part 1)","volume":"26","author":"Kim","year":"2016","journal-title":"Expert Opin. Ther. Pat"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1038\/sj.bjp.0705681","article-title":"Antianxiety and Antidepressant-like Effects of AC-5216, a Novel Mitochondrial Benzodiazepine Receptor Ligand","volume":"142","author":"Kita","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.str.2010.03.001","article-title":"Three-Dimensional Structure of TspO by Electron Cryomicroscopy of Helical Crystals","volume":"18","author":"Korkhov","year":"2010","journal-title":"Structure"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1016\/j.bcp.2004.06.040","article-title":"GABA(A) Agonists and Partial Agonists: THIP (Gaboxadol) as a Non-opioid Analgesic and a Novel Type of Hypnotic","volume":"68","author":"Krogsgaard-Larsen","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.tips.2019.11.005","article-title":"Insight into the Structural Features of TSPO: Implications for Drug Development","volume":"41","author":"Lacapere","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1159\/000119017","article-title":"Cortical and Subcortical EEG in Relation to Sleep-Wake Behavior in Mammalian Species","volume":"28","author":"Lancel","year":"1993","journal-title":"Neuropsychobiology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2852","DOI":"10.1002\/(sici)1521-3773(19991004)38:19<2852::aid-anie2852>3.0.co;2-z","article-title":"Sleep and its Modulation by Drugs that Affect GABA(A) Receptor Function","volume":"38","author":"Lancel","year":"1999","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B40","doi-asserted-by":"publisher","first-page":"10809","DOI":"10.1523\/JNEUROSCI.1487-12.2012","article-title":"Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging","volume":"32","author":"Lavisse","year":"2012","journal-title":"J. Neurosci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1016\/0024-3205(83)90063-2","article-title":"Peripheral Benzodiazepine Binding Sites: Effect of PK 11195, 1-(2-Chlorophenyl)-N-Methyl-(1-Methylpropyl)-3 Isoquinolinecarboxamide. II. In Vivo Studies","volume":"32","author":"Le Fur","year":"1983","journal-title":"Life Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.bbrc.2016.04.080","article-title":"A Translocator Protein 18 kDa Ligand, Ro5-4864, Inhibits ATP-Induced NLRP3 Inflammasome Activation","volume":"474","author":"Lee","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B43","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1126\/science.126059010.1126\/science.aab2595","article-title":"Response to Comment on \"Crystal Structures of Translocator Protein (TSPO) and Mutant Mimic of a Human Polymorphism\"","volume":"350","author":"Li","year":"","journal-title":"Science"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1111\/1440-1681.12460","article-title":"Neuroprotective Effects of a Novel Translocator Protein (18 kDa) Ligand, ZBD-2, against Focal Cerebral Ischemia and NMDA-Induced Neurotoxicity","volume":"42","author":"Li","year":"","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1515\/bmc-2012-0033","article-title":"Neurosteroids and GABAergic Signaling in Health and Disease","volume":"4","author":"MacKenzie","year":"2013","journal-title":"Biomol. Concepts"},{"key":"B46","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.brainres.2007.04.054","article-title":"Phase-dependent Roles of Reactive Microglia and Astrocytes in Nervous System Injury as Delineated by Imaging of Peripheral Benzodiazepine Receptor","volume":"1157","author":"Maeda","year":"2007","journal-title":"Brain Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1093\/sleep\/20.11.939","article-title":"Topographical Distribution of Spindles and K-Complexes in normal Subjects","volume":"20","author":"McCormick","year":"1997","journal-title":"Sleep"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1152\/jn.00450.2011","article-title":"Molecular Basis for the High THIP\/gaboxadol Sensitivity of Extrasynaptic GABA(A) Receptors","volume":"106","author":"Meera","year":"2011","journal-title":"J. Neurophysiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.mce.2013.04.014","article-title":"Steroid Hormone Synthesis in Mitochondria","volume":"379","author":"Miller","year":"2013","journal-title":"Mol. Cel Endocrinol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s11940-016-0401-x","article-title":"The Role of Benzodiazepines in the Treatment of Epilepsy","volume":"18","author":"Ochoa","year":"2016","journal-title":"Curr. Treat. Options. Neurol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s13054-016-1294-5","article-title":"Optimizing Sedation in Patients with Acute Brain Injury","volume":"20","author":"Oddo","year":"2016","journal-title":"Crit. Care"},{"key":"B52","doi-asserted-by":"publisher","first-page":"24","DOI":"10.2967\/jnumed.110.079459","article-title":"Mixed-Affinity Binding in Humans with 18-kDa Translocator Protein Ligands","volume":"52","author":"Owen","year":"2011","journal-title":"J. Nucl. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.tips.2006.06.005","article-title":"Translocator Protein (18kDa): New Nomenclature for the Peripheral-type Benzodiazepine Receptor Based on its Structure and Molecular Function","volume":"27","author":"Papadopoulos","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12500","article-title":"Translocator Protein (18 kDa): an Update on its Function in Steroidogenesis","volume":"30","author":"Papadopoulos","year":"2018","journal-title":"J. Neuroendocrinol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3181\/00379727-217-44215","article-title":"Structure and Function of the Peripheral-type Benzodiazepine Receptor in Steroidogenic Cells","volume":"217","author":"Papadopoulos","year":"1998","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.resuscitation.2018.03.025","article-title":"Comparison of Two Sedation Regimens during Targeted Temperature Management after Cardiac Arrest","volume":"128","author":"Paul","year":"2018","journal-title":"Resuscitation"},{"key":"B57","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0024-3205(84)90106-1","article-title":"Behavioural Actions of Ro 5-4864: A Peripheral-type Benzodiazepine?","volume":"35","author":"Pellow","year":"","journal-title":"Life Sci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1007\/BF00428536","article-title":"Multiple Sites of Action for Anxiogenic Drugs: Behavioural, Electrophysiological and Biochemical Correlations","volume":"83","author":"Pellow","year":"","journal-title":"Psychopharmacology (Berl)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3389\/fnsys.2016.00030","article-title":"Making Waves in the Brain: What Are Oscillations, and Why Modulating Them Makes Sense for Brain Injury","volume":"10","author":"Pevzner","year":"2016","journal-title":"Front. Syst. Neurosci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1038\/nrd3295","article-title":"Translocator Protein (18 kDa) (TSPO) as a Therapeutic Target for Neurological and Psychiatric Disorders","volume":"9","author":"Rupprecht","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"B61","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1126\/science.1175055","article-title":"Translocator Protein (18 kD) as Target for Anxiolytics without Benzodiazepine-like Side Effects","volume":"325","author":"Rupprecht","year":"2009","journal-title":"Science"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15622975.2021.1961503","article-title":"Neuroinflammation and Psychiatric Disorders: Relevance of C1q, Translocator Protein (18 kDa) (TSPO), and Neurosteroids","author":"Rupprecht","year":"2021","journal-title":"World J. Biol. Psychiatry"},{"key":"B63","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1210\/me.2015-1033","article-title":"Minireview: Translocator Protein (TSPO) and Steroidogenesis: A Reappraisal","volume":"29","author":"Selvaraj","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/sj.bjp.0702530","article-title":"2-Phenyl-imidazo[1,2-a]pyridine Derivatives as Ligands for Peripheral Benzodiazepine Receptors: Stimulation of Neurosteroid Synthesis and Anticonflict Action in Rats","volume":"127","author":"Serra","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.expneurol.2008.08.008","article-title":"Neuroprotective Effect of Ro5-4864 Following Brain Injury","volume":"214","author":"Soustiel","year":"2008","journal-title":"Exp. Neurol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"14439","DOI":"10.1073\/pnas.2435457100","article-title":"Neuroactive Steroids Reduce Neuronal Excitability by Selectively Enhancing Tonic Inhibition Mediated by delta Subunit-Containing GABAA Receptors","volume":"100","author":"Stell","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B67","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S0165-0173(01)00135-7","article-title":"Role of Pregnenolone, Dehydroepiandrosterone and Their Sulfate Esters on Learning and Memory in Cognitive Aging","volume":"37","author":"Vall\u00e9e","year":"2001","journal-title":"Brain Res. Rev."},{"key":"B68","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.neuropharm.2004.03.017","article-title":"Effects of Diazepam and Zolpidem on EEG Beta Frequencies Are Behavior-specific in Rats","volume":"47","author":"van Lier","year":"2004","journal-title":"Neuropharmacology"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1523\/jneurosci.20-05-01982.2000","article-title":"Neuroactive Steroid 3alpha-Hydroxy-5alpha-Pregnan-20-One Modulates Electrophysiological and Behavioral Actions of Ethanol","volume":"20","author":"VanDoren","year":"2000","journal-title":"J. Neurosci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.jalz.2014.08.105","article-title":"Imaging Neuroinflammation in Alzheimer's Disease and Other Dementias: Recent Advances and Future Directions","volume":"11","author":"Varley","year":"2015","journal-title":"Alzheimers Dement"},{"key":"B71","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.pharmthera.2005.09.007","article-title":"The Peripheral-type Benzodiazepine Receptor and the Cardiovascular System. Implications for Drug Development","volume":"110","author":"Veenman","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"B72","doi-asserted-by":"publisher","first-page":"E7586","DOI":"10.3390\/ijms21207586","article-title":"Raloxifene as Treatment for Various Types of Brain Injuries and Neurodegenerative Diseases: A Good Start","volume":"21","author":"Veenman","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/1098-2299(200007\/08)50:3\/4<355::AID-DDR18>3.0.CO10.1002\/1098-2299(200007\/08)50:3\/4<355::aid-ddr18>3.0.co;2-w","article-title":"Peripheral-type Benzodiazepine Receptors: Their Implication in Brain Disease","volume":"50","author":"Veenman","year":"2000","journal-title":"Drug Dev. Res"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1073\/pnas.84.8.2256","article-title":"Porphyrins Are Endogenous Ligands for the Mitochondrial (Peripheral-type) Benzodiazepine Receptor","volume":"84","author":"Verma","year":"1987","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B75","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev.pa.29.040189.001515","article-title":"Peripheral Type Benzodiazepine Receptors","volume":"29","author":"Verma","year":"1989","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/0165-0173(95)00002-k","article-title":"Contingent Tolerance to the Anticonvulsant Effects of Carbamazepine: Relationship to Loss of Endogenous Adaptive Mechanisms","volume":"20","author":"Weiss","year":"1995","journal-title":"Brain Res. Brain Res. Rev."},{"key":"B77","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.bbrc.2003.10.070","article-title":"Protoporphyrin IX Binding and Transport by Recombinant Mouse PBR","volume":"311","author":"Wendler","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B78","doi-asserted-by":"publisher","first-page":"E3161","DOI":"10.3390\/ijms20133161","article-title":"Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders","volume":"20","author":"Werry","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1111\/j.1460-9568.2007.05455.x","article-title":"The EEG Effects of THIP (Gaboxadol) on Sleep and Waking Are Mediated by the GABA(A)delta-subunit-containing Receptors","volume":"25","author":"Winsky-Sommerer","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"e71258","DOI":"10.1371\/journal.pone.0071258","article-title":"The 18-kDa Translocator Protein (TSPO) Disrupts Mammary Epithelial Morphogenesis and Promotes Breast Cancer Cell Migration","volume":"8","author":"Wu","year":"2013","journal-title":"PLOS ONE"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10877-z","article-title":"Neuroinflammation in Parkinson's Disease: a Meta-Analysis of PET Imaging Studies","author":"Zhang","year":"2021","journal-title":"J. Neurol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"11929","DOI":"10.1523\/JNEUROSCI.1860-14.2014","article-title":"An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex","volume":"34","author":"Zhang","year":"2014","journal-title":"J. Neurosci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.750554\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T08:35:44Z","timestamp":1649061344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.750554\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,4]]},"references-count":82,"alternative-id":["10.3389\/fphar.2022.750554"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.750554","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,4]]},"article-number":"750554"}}