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The Effect of 5-HT1A Receptor Antagonist on Reward-Based
The Journal of Physiological Sciences (2019) 69:1057–1069 https://doi.org/10.1007/s12576-019-00725-1 ORIGINAL PAPER The efect of 5‑HT1A receptor antagonist on reward‑based decision‑making Fumika Akizawa1 · Takashi Mizuhiki1,2 · Tsuyoshi Setogawa1,2 · Mai Takafuji1 · Munetaka Shidara1,2 Received: 5 July 2019 / Accepted: 27 October 2019 / Published online: 8 November 2019 © The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019 Abstract When choosing the best action from several alternatives, we compare each value that depends on the balance between beneft and cost. Previous studies have shown that animals and humans with low brain serotonin (5-HT) level tend to choose smaller immediate reward. We used a decision-making schedule task to investigate whether 5-HT1A receptor is responsible for the decisions related to reward. In this task, the monkeys chose either of two diferent alternatives that were comprised of 1–4 drops of liquid reward (beneft) and 1–4 repeats of a color discrimination trial (workload cost), then executed the chosen schedule. By the administration of 5-HT1A antagonist, WAY100635, the choice tendency did not change, however, the sen- sitivity to the amount of reward in the schedule part was diminished. The 5-HT1A could have a role in maintaining reward value to keep track with the promised reward rather than modulating workload discounting of reward value. Keywords 5-HT1A · Value discounting · WAY100635 · Decision-making · Workload · Rhesus monkey Introduction comprises an iteration of simple color discriminations. The monkey can choose one of two diferent schedules to earn Whenever we choose an option from two or more alterna- promised reward. -
Subanesthetic Doses of Ketamine Transiently Decrease Serotonin Transporter Activity: a PET Study in Conscious Monkeys
Neuropsychopharmacology (2013) 38, 2666–2674 & 2013 American College of Neuropsychopharmacology. All rights reserved 0893-133X/13 www.neuropsychopharmacology.org Subanesthetic Doses of Ketamine Transiently Decrease Serotonin Transporter Activity: A PET Study in Conscious Monkeys 1 1 1 1 1 Shigeyuki Yamamoto , Hiroyuki Ohba , Shingo Nishiyama , Norihiro Harada , Takeharu Kakiuchi , 1 ,2 Hideo Tsukada and Edward F Domino* 1 2 Central Research Laboratory, Hamamatsu Photonics KK, Hamakita, Japan; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA Subanesthetic doses of ketamine, an N-methyl-D-aspartic acid (NMDA) antagonist, have a rapid antidepressant effect which lasts for up to 2 weeks. However, the neurobiological mechanism regarding this effect remains unclear. In the present study, the effects of subanesthetic doses of ketamine on serotonergic systems in conscious monkey brain were investigated. Five young monkeys 11 underwent four positron emission tomography measurements with [ C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)benzoni- 11 trile ([ C]DASB) for the serotonin transporter (SERT), during and after intravenous infusion of vehicle or ketamine hydrochloride in a 11 dose of 0.5 or 1.5 mg/kg for 40 min, and 24 h post infusion. Global reduction of [ C]DASB binding to SERT was observed during ketamine infusion in a dose-dependent manner, but not 24 h later. The effect of ketamine on the serotonin 1A receptor (5-HT1A-R) and dopamine transporter (DAT) was also investigated in the same subjects studied with [11C]DASB. No significant changes were observed in either 5-HT -R or DAT binding after ketamine infusion. Microdialysis analysis indicated that ketamine infusion transiently increased 1A serotonin levels in the extracellular fluid of the prefrontal cortex. -
United States Patent (19) 11 Patent Number: 5,902,815 Olney Et Al
USOO5902815A United States Patent (19) 11 Patent Number: 5,902,815 Olney et al. (45) Date of Patent: May 11, 1999 54 USE OF 5HT2A SEROTONIN AGONISTS TO Hougaku, H. et al., “Therapeutic effect of lisuride maleate on PREVENT ADVERSE EFFECTS OF NMDA post-stroke depression” Nippon Ronen Igakkai ZaSShi 31: RECEPTOR HYPOFUNCTION 52-9 (1994) (abstract). Kehne, J.H. et al., “Preclinical Characterization of the Poten 75 Inventors: John W. Olney, Ladue; Nuri B. tial of the Putative Atypical Antipsychotic MDL 100,907 as Farber, University City, both of Mo. a Potent 5-HT2A Antagonist with a Favorable CNS Saftey Profile.” The Journal of Pharmacology and Experimental 73 Assignee: Washington University, St. Louis, Mo. Therapuetics 277: 968–981 (1996). Maurel-Remy, S. et al., “Blockade of phencyclidine-induced 21 Appl. No.: 08/709,222 hyperlocomotion by clozapine and MDL 100,907 in rats reflects antagonism of 5-HT2A receptors' European Jour 22 Filed: Sep. 3, 1996 nal of Pharmacology 280: R9–R11 (1995). 51) Int. Cl. ........................ A61K 31/445; A61K 31/54; Olney, J.W., et al., “NMDAantagonist neurotoxicity: Mecha A61K 31/135 nism and prevention,” Science 254: 1515–1518 (1991). 52 U.S. Cl. .......................... 514/285; 514/315; 514/318; Olney, J.W., et al., “Glutamate receptor dysfunction and 514/646 schizophrenia.” Arch. Gen. Psychiatry 52:998-1007 (1995). 58 Field of Search ............................. 514/285; 314/315, Pulvirenti, L. et al., “Dopamine receptor agonists, partial 314/318, 646 agonists and psychostimulant addiction' Trends Pharmacol Sci 15: 374-9 (1994). 56) References Cited Robles, R.G. et al., “Natriuretic Effects of Dopamine Agonist Drugs in Models of Reduced Renal Mass” Journal of U.S. -
Fushi-Tarazu During Segmentation
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 5441-5445, June 1995 Developmental Biology Drosophila 5-HT2 serotonin receptor: Coexpression with fushi-tarazu during segmentation (in situ hybridization/G protein-coupled receptors/pair-rule gene) JEAN-FRAN;OIS CoLAs*, JEAN-MARIE LAUNAYt, ODILE KELLERMANNt, PHILIPPE ROSAY*, AND Luc MAROTEAUX*§ *Institut de Genetique et de Biologie Mol6culaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale, Universite de Strasbourg, BP 163, 67404 Illkirch Cedex, France; tH6pital Lariboisiere, Service de Biochimie, 2 rue Ambroise Pare, 75475 Paris Cedex 10, France; and tDepartement de Biologie Moleculaire, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France Communicated by Walter J. Gehring, University ofBasel, Basel, Switzerland, March 6, 1995 (received for review December 5, 1994) ABSTRACT Serotonin, first described as a neurotrans- ergic neurons (6), and to incomplete sclerotization of the mitter in invertebrates, has been investigated mostly for its cuticule (3). functions in the mature central nervous system of higher We report the characterization of a Drosophila serotonin vertebrates. Serotonin receptor diversity has been described receptor that displays a typical 5-HT2 receptor sequence, gene in the mammalian brain and in insects. We report the isolation organization, and pharmacology.5 It is expressed in the central of a cDNA coding for a Drosophila melanogaster serotonin nervous system (CNS) during larval and adult stages. More receptor that displays a sequence, a gene organization, and surprisingly, this receptor is expressed at the blastoderm stage pharmacological properties typical of the mammalian 5-HT2 of embryogenesis in a pattern similar to that of the pair-rule serotonin receptor subtype. -
(12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO). -
Among a Series of Novel D4 Dopamine Receptor Agonists and Antagonists Jeremiah J
Topographically Based Search for an “Ethogram” Among a Series of Novel D4 Dopamine Receptor Agonists and Antagonists Jeremiah J. Clifford, Ph.D., and John L. Waddington, Ph.D., D.Sc. The effects of three selective D4 antagonists [CP-293,019, 25.0 mg/kg) failed to influence any behavior; whereas, PD L-745,870, and Ro 61-6270] and two putative selective D4 168077 (0.2–25.0 mg/kg) induced nonstereotyped shuffling agonists [CP-226,269 and PD 168077] were compared with locomotion with uncoordinated movements, jerking, and those of the generic D2-like [D2L/S,D3, D4] antagonist yawning, which were insensitive to antagonism by haloperidol to identify any characteristic “ethogram,” in CP-293,019, L-745,870, or haloperidol. These findings fail terms of individual topographies of behavior within the to indicate any “ethogram” for selective manipulation of D4 natural rodent repertoire, as evaluated using ethologically receptor function at the level of the interaction between based approaches. Among the D4 antagonists, neither motoric and psychological processes in sculpting behavioral L-745,870 (0.0016–1.0 mg/kg) nor Ro 61-6270 (0.2–25.0 topography over habituation of exploration through to mg/kg) influenced any behavior; whereas, CP-293,019 quiescence and focus attention on social, cognitive, or other (0.2–25.0 mg/kg) induced episodes of nonstereotyped levels of examination. sniffing, sifting, and vacuous chewing; there were no [Neuropsychopharmacology 22:538–544, 2000] consistent effects on responsivity to the D2-like agonist RU © 2000 American College of Neuropsychopharmacology. 24213. Among the putative D4 agonists, CP-226,269 (0.2– Published by Elsevier Science Inc. -
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss
Supplemental Material can be found at: /content/suppl/2020/12/18/73.1.202.DC1.html 1521-0081/73/1/202–277$35.00 https://doi.org/10.1124/pharmrev.120.000056 PHARMACOLOGICAL REVIEWS Pharmacol Rev 73:202–277, January 2021 Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: MICHAEL NADER Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss Antonio Inserra, Danilo De Gregorio, and Gabriella Gobbi Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada Abstract ...................................................................................205 Significance Statement. ..................................................................205 I. Introduction . ..............................................................................205 A. Review Outline ........................................................................205 B. Psychiatric Disorders and the Need for Novel Pharmacotherapies .......................206 C. Psychedelic Compounds as Novel Therapeutics in Psychiatry: Overview and Comparison with Current Available Treatments . .....................................206 D. Classical or Serotonergic Psychedelics versus Nonclassical Psychedelics: Definition ......208 Downloaded from E. Dissociative Anesthetics................................................................209 F. Empathogens-Entactogens . ............................................................209 -
Pharmaceuticals Appendix
)&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ADAPALENE 106685-40-9 ABANOQUIL 90402-40-7 ADAPROLOL 101479-70-3 ABECARNIL 111841-85-1 ADEMETIONINE 17176-17-9 ABLUKAST 96566-25-5 ADENOSINE PHOSPHATE 61-19-8 ABUNIDAZOLE 91017-58-2 ADIBENDAN 100510-33-6 ACADESINE 2627-69-2 ADICILLIN 525-94-0 ACAMPROSATE 77337-76-9 ADIMOLOL 78459-19-5 ACAPRAZINE 55485-20-6 ADINAZOLAM 37115-32-5 ACARBOSE 56180-94-0 ADIPHENINE 64-95-9 ACEBROCHOL 514-50-1 ADIPIODONE 606-17-7 ACEBURIC ACID 26976-72-7 ADITEREN 56066-19-4 ACEBUTOLOL 37517-30-9 ADITOPRIME 56066-63-8 ACECAINIDE 32795-44-1 ADOSOPINE 88124-26-9 ACECARBROMAL 77-66-7 ADOZELESIN 110314-48-2 ACECLIDINE 827-61-2 ADRAFINIL 63547-13-7 ACECLOFENAC 89796-99-6 ADRENALONE 99-45-6 ACEDAPSONE 77-46-3 AFALANINE 2901-75-9 ACEDIASULFONE SODIUM 127-60-6 AFLOQUALONE 56287-74-2 ACEDOBEN 556-08-1 AFUROLOL 65776-67-2 ACEFLURANOL 80595-73-9 AGANODINE 86696-87-9 ACEFURTIAMINE 10072-48-7 AKLOMIDE 3011-89-0 ACEFYLLINE CLOFIBROL 70788-27-1 -
Ligand-Based Pharmacophore Studies in the Dopaminergic System Amar P
University of Wollongong Research Online University of Wollongong Thesis Collection University of Wollongong Thesis Collections 2011 Ligand-based pharmacophore studies in the dopaminergic system Amar P. Inamdar University of Wollongong Recommended Citation Inamdar, Amar P., Ligand-based pharmacophore studies in the dopaminergic system, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2011. http://ro.uow.edu.au/theses/3535 Research Online is the open access institutional repository for the University of Wollongong. For further information contact Manager Repository Services: [email protected]. LIGAND-BASED PHARMACOPHORE STUDIES IN THE DOPAMINERGIC SYSTEM A thesis submitted in partial fulfilment of the requirements for the award of the degree DOCTOR OF PHILOSOPHY From UNIVERSITY OF WOLLONGONG By AMAR P. INAMDAR, B.PHARM., M.PHARM. SCHOOL OF CHEMISTRY November 2011 THESIS CERTIFICATION I, Amar P. Inamdar, declare that this thesis, submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy, in the School of Chemistry, University of Wollongong, is wholly my own work unless otherwise referenced or acknowledged. The document has not been submitted for qualifications at any other academic institution. Amar P. Inamdar November 2011 i ACKNOWLEDGEMENTS I am truly grateful to my supervisor, Prof. John B. Bremner, whose support, encouragement and guidance has helped me immensely in the completion of this project. Most importantly, I am thankful for his patience over all these years and believing in me in spite of various difficult periods in this journey. I know he has sacrificed a significant amount of his personal time to make this happen. I also owe my deepest gratitude to Associate Prof. -
Dopamine D2 Receptors in the Cerebral Cortex
Proc. Nati. Acad. Sci. USA Vol. 86, pp. 6412-6416, August 1989 Neurobiology Dopamine D2 receptors in the cerebral cortex: Distribution and pharmacological characterization with [3Hlraclopride (raclopride binding/neostriatum/rat/monkey) MICHAEL S. LIDOW*t, PATRICIA S. GOLDMAN-RAKIC*, PASKO RAKIC*, AND ROBERT B. INNIS*f Section of *Neuroanatomy and tDepartment of Psychiatry, Yale University, School of Medicine, New Haven, CT 06510 Contributed by Pasko Rakic, May 17, 1989 ABSTRACT An apparent involvement of dopamine in the MATERIALS AND METHODS regulation of cognitive functions and the recognition of a widespread dopaminergic innervation of the cortex have fo- Tissue was obtained from three adult rhesus monkeys cused attention on the identity of cortical dopamine receptors. (Macaca mulatta): one male and two females. The animals However, only the presence and distribution of dopamine DI were anesthesized with sodium pentobarbital (40 mg/kg) and receptors in the cortex have been well documented. Compa- perfused with ice-cold phosphate-buffered saline followed by rable information on cortical D2 sites is lacking. We report here 0.1% paraformaldehyde (9; 15). The cerebral cortex and the results of binding studies in the cortex and neostriatum of neostriatum were rapidly removed and immersed in isopen- rat and monkey using the D2 selective antagonist [3H]raclo- tane at -700C for 5 min before storing at -800C until use. For pride. In both structures [3H]raclopride bound in a sodium- competition studies tissue was pooled from several neocor- dependent and saturable manner to a single population of sites tical areas. However, saturation studies were conducted on with pharmacological profiles of dopamine D2 receptors. -
Metabolic Changes in the Rodent Brain After Acute Administration of Salvinorin a Jacob M
B Academy of Molecular Imaging, 2009 Mol Imaging Biol (2009) 11:137Y143 Published Online: 9 January 2009 DOI: 10.1007/s11307-008-0192-x BRIEF ARTICLE Metabolic Changes in the Rodent Brain after Acute Administration of Salvinorin A Jacob M. Hooker,1 Vinal Patel,1 Shiva Kothari,1 Wynne K. Schiffer1 Medical Department, Brookhaven National Laboratory, Upton, NY, 11973, USA Abstract Purpose: Salvinorin A (SA) is a potent and highly selective kappa-opioid receptor (KOR) agonist with rapid kinetics and commensurate behavioral effects; however, brain regions associated with these effects have not been determined. Procedures: Freely moving adult male rats were given SA intraperitoneally during uptake and trapping of the brain metabolic radiotracer, 2-deoxy-2-[F-18]fluoro-D-glucose (FDG), followed by image acquisition in a dedicated animal positron emission tomography (PET) system. Age-matched control animals received vehicle treatment. Animal behavior during FDG uptake was recorded digitally and later analyzed for locomotion. Group differences in regional FDG uptake normalized to whole brain were determined using Statistical Parametric Mapping (SPM) and verified by region of interest (ROI) analysis. Results: SA-treated animals demonstrated significant increases in FDG uptake compared to controls in several brain regions associated with the distribution of KOR such as the periaqueductal grey, bed nucleus of the stria terminalis and the cerebellar vermis, as well as in the hypothalamus. Significant bilateral activations were also observed in the auditory, sensory, and frontal cortices. Regional decreases in metabolic demand were observed bilaterally in the dorsolateral striatum and hippocampus. Locomotor activity did not differ between SA and vehicle during FDG uptake. -
Decrease in Brain Serotonin 2 Receptor Binding In
ORIGINAL ARTICLE Decrease in Brain Serotonin 2 Receptor Binding in Patients With Major Depression Following Desipramine Treatment A Positron Emission Tomography Study With Fluorine-18–Labeled Setoperone Lakshmi N. Yatham, MBBS, FRCPC; Peter F. Liddle, PhD, MBBS; Joelle Dennie, MSc; I-Shin Shiah, MD; Michael J. Adam, PhD; Carol J. Lane, MSc; Raymond W. Lam, MD; Thomas J. Ruth, PhD Background: The neuroreceptor changes involved in Results: Eight of the 10 patients responded to desipra- therapeutic efficacy of various antidepressants remain un- mine treatment as indicated by more than 50% decrease clear. Preclinical studies have shown that long-term ad- in Hamilton Depression Rating Scale scores. Depressed ministration of various antidepressants causes down- patients showed a significant decrease in 5-HT2 recep- regulation of brain serotonin 2 (5-HT2) receptors in rodents, tor binding as measured by setoperone binding in fron- but it is unknown if similar changes occur following anti- tal, temporal, parietal, and occipital cortical regions fol- depressant treatment in depressed patients. Our purpose, lowing desipramine treatment. The decrease in 5-HT2 therefore, was to assess the effects of treatment with desi- receptor binding was observed bilaterally and was par- pramine hydrochloride on brain 5-HT2 receptors in de- ticularly prominent in frontal cortex. pressed patients using positron emission tomography (PET) and fluorine-18 (18F)–labeled setoperone. Conclusions: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain fol- Methods: Eleven patients who met DSM-IV criteria for lowing desipramine treatment, but it is unknown if this major depression as determined by a structured clinical change in 5-HT2 receptors is due to clinical improve- interview for DSM-III-R diagnosis and suitable for treat- ment or an effect of desipramine that is unrelated to clini- ment with desipramine were recruited.