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      Brain Mediation of Anolis Social Dominance Displays

      research-article
      .a-f
      Brain, Behavior and Evolution
      S. Karger AG
      5-HT1B , 5-HT1D, Dominance, Submission, Anolis, Serotonin, Territoriality

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          Abstract

          Measures of serotonin (5-HT) turnover in A. carolinensis forebrain increase acutely when males exhibit dominant social/territorial display routines, but decrease during submissive displays [Baxter et al., 2001a, b]. The present investigation sought to determine whether a difference in presynaptic regulatory receptors – one that might affect 5-HT flux – distinguish dominant vs. submissive anoles. Both 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors are presynaptic regulators of output; this role is prominent at 5-HT terminals, where stimulation inhibits 5-HT release. Here, <sup>3</sup>H-sumatriptan binding at sites similar to mammalian 5-HT<sub>1B/D</sub> receptors was significantly higher in forebrain regions of submissive anoles than in dominant cagemates; this receptor site seemed pharmacologically more like a 5-HT<sub>1B</sub> than a 5-HT<sub>1D</sub> receptor. Higher densities of presynaptic 5-HT<sub>1B</sub> receptors in subordinates than in dominants might account for differences in 5-HT flux (lower in subordinates than in dominants) observed in displaying anoles of different status. Knockout mice missing the 5-HT<sub>1B</sub> receptor show heightened male territorial aggressiveness, thus similar 5-HT regulatory mechanisms might influence the likelihood of dominance in both mammals and reptiles.

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          Most cited references14

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          A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635.

          WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride) is an achiral phenylpiperazine derivative that binds with high affinity and selectivity to the 5-HT1A receptor. WAY-100635 displaced specific binding of the 5-HT1A radioligand, [3H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), to rat hippocampal membranes with a pIC50 of 8.87. This represented a greater than 100-fold selectivity relative to binding at other 5-HT receptor subtypes and major neurotransmitter receptor, reuptake and ion channel sites. In functional assays, WAY-100635 was a potent 5-HT1A receptor antagonist, with no evidence of any 5-HT1A receptor agonist or partial agonist activity. In the isolated guinea-pig ileum WAY-100635 was a potent and, at high concentrations, an insurmountable antagonist of the 5-HT1A receptor agonist action of 5-carboxamidotryptamine, with an apparent pA2 value (at 0.3 nM) of 9.71. WAY-100635 blocked the inhibitory action of 8-OH-DPAT on dorsal raphe neuronal firing in the anaesthetised rat at doses which had no inhibitory action per se. In behavioural models, WAY-100635 itself induced no overt behavioural changes but potently antagonised the behavioural syndrome induced by 8-OH-DPAT in the rat and guinea-pig (minimum effective dose = 0.003 mg/kg s.c. and ID50 = 0.01 mg/kg s.c., respectively). WAY-100635 also blocked the hypothermia induced by 8-OH-DPAT in the mouse and rat with ID50 values of 0.01 mg/kg s.c. These data indicate that WAY-100635 will be used as a standard antagonist in further studies of 5-HT1A receptor function.
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            5-Hydroxytryptamine receptor subtypes in vertebrates and invertebrates.

            In the last few years, molecular biology has led to the cloning and characterization of several 5-HT receptors (serotonin receptors) in vertebrates and in invertebrates. These studies have allowed identification not only of 5-HT receptors already described but also of novel subtypes. The molecular cloning of 13 different mammalian receptor subtypes revealed an unexpected heterogeneity among 5-HT receptors. Except for the 5-HT3 receptors which are ligand-gated ion channel receptors, all the other 5-HT receptors belong to the large family of receptors interacting with G proteins. Based on their amino acid sequence homology and coupling to second messengers these receptors can be divided into distinct families: the 5-HT1 family contains receptors that are negatively coupled to adenylate cyclase: the 5-HT2 family includes receptors that stimulate phospholipase C; the adenylyl cyclase stimulatory receptors are a heterogeneous group including the 5-HT4 receptor which has not yet been cloned, the Drosophila 5-HTdro1 receptor and two mammalian receptors tentatively named 5-HT6 and 5-HT7 receptors. The 5-HT5A and 5-HT5B receptors might constitute a new family of 5-HT receptors whose effectors are unknown. This review focusses on the molecular characteristics of the cloned 5-HT receptors such as their structure, their effector systems and their distribution within the central nervous system. The existence of a large number of receptors with distinct signalling properties and expression patterns might enable a single substance like 5-HT to generate simultaneously a large panel of effects in many brain structures. The availability of the genes encoding these receptors has already allowed a partial characterization of their structure-function relationship and will probably allow in the future a dissection of the contribution of each of these receptor subtypes to physiology and behaviour.
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              Functional characteristics of heterologously expressed 5-HT receptors.

              Over the past 10 years, molecular cloning has revealed the presence of 15 serotonin (5-hydroxytryptamine; 5-HT) receptor subtypes, which can be subdivided in seven subfamilies. Except for the 5-HT3 receptors, which are ligand-gated ion channels, all 5-HT receptors belong to the superfamily of G-protein-coupled receptors. The large multiplicity of 5-HT receptor subtypes has been suggested to be a direct result of the evolutionary age of the 5-HT system. Molecular information on G-protein-coupled 5-HT receptors is currently available for several mammalian species as well as for a limited number of invertebrate species (insects, molluscs). The aim of this review is to give an overview of all cloned 5-HT receptor subtypes belonging to the superfamily of G-protein-coupled receptors with specific emphasis on the pharmacological and signaling properties of the receptors upon expression in several heterologous expression systems.
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                Author and article information

                Journal
                BBE
                Brain Behav Evol
                10.1159/issn.0006-8977
                Brain, Behavior and Evolution
                S. Karger AG
                0006-8977
                1421-9743
                2001
                April 2001
                28 September 2001
                : 57
                : 4
                : 202-213
                Affiliations
                aDepartment of Psychiatry and Behavioral Neurobiology, bDepartment of Neurobiology, cDepartment of Psychology, University of Alabama at Birmingham, Ala. (UAB), dDepartment of Molecular and Medical Pharmacology, eDepartment of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Calif. (UCLA), and fYerkes Primate Center, Atlanta, Ga., USA
                Article
                47237 Brain Behav Evol 2001;57:202–213
                10.1159/000047237
                11641558
                e7f39293-88a3-45cd-b05e-35262932f678
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 6, References: 50, Pages: 12
                Categories
                Original Paper

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Submission,5-HT1D,Anolis,5-HT1B ,Dominance,Serotonin,Territoriality

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