Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268

272 Pages·2005·2.4 MB·English

by  Novartis Foundation(eds.)

Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268, Volume 268.
Edited by Gregory Bock and Jamie Goode
Copyright  Novartis Foundation 2005. ISBN: 0-470-01068-1
MOLECULAR
MECHANISMS
INFLUENCING
AGGRESSIVE
BEHAVIOURS
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Novartis Foundation Symposium 268
MOLECULAR
MECHANISMS
INFLUENCING
AGGRESSIVE
BEHAVIOURS
2005
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Contents
SymposiumonMolecularmechanismsin£uencingaggressivebehaviours,heldattheNovartis
Foundation,London,20^22July2004
Editors:GregoryBock(Organizer)andJamieGoode
ThismeetingwasbasedonaproposalmadebyDonaldPfa¡,BarryKeverneandRandyNelson
DonaldPfa¡ Introduction 1
RobertJ.BlanchardandD.CarolineBlanchard Somesuggestionsforrevitalizing
aggressionresearch 4
Discussion 13
RobinLovell-Badge Aggressivebehaviour:contributionsfromgenesonthe
Ychromosome 20
Discussion 33
DianeM.Robins Androgenreceptorandmolecularmechanismsofmale-speci¢c
geneexpression 42
Discussion 53
EdwardS.Brodkin Quantitativetraitlocusanalysisofaggressivebehavioursin
mice 57
Discussion 69
DonaldPfa¡,ElenaCholerisandSonokoOgawa Genesforsexhormone
receptorscontrollingmouseaggression 78
Discussion 89
GeneraldiscussionI 96
CatherineDulac Moleculararchitectureofpheromonesensinginmammals 100
Discussion 107
Klaus-PeterLesch Serotonergicgeneinactivationinmice:modelsforanxietyand
aggression? 111
Discussion 140
v
vi CONTENTS
RandyJ.Nelson E¡ectsofnitricoxideontheHPAaxisandaggression 147
Discussion 160
GeneraldiscussionII 167
BerendOlivier Serotonergicmechanismsinaggression 171
Discussion 183
CraigF.Ferris Vasopressin/oxytocinandaggression 190
Discussion 198
ManuelaMartinezandConcepcio¤nBlasco-Ros Typologyofhumanaggression
anditsbiologicalcontrol 201
Discussion 208
StephenJ.Suomi Aggressionandsocialbehaviourinrhesusmonkeys 216
Discussion 222
IanW.Craig TheroleofmonoamineoxidaseA(MAOA)intheaetiologyof
antisocialbehaviour:theimportanceofgene^environmentinteractions 227
Discussion 237
Finaldiscussion 242
Indexofcontributors 254
Subjectindex 256
Participants
D.CarolineBlanchard UniversityofHawaii,DepartmentofPsychology,
CollegeofSocialSciences,Gartley110,2430CampusRoad,Honolulu,
HI96822,USA
RobertJ.Blanchard UniversityofHawaii,DepartmentofPsychology,College
ofSocialSciences,Gartley110,2430CampusRoad,Honolulu,HI96822,USA
Bj˛rnBrembs InstitutfˇrNeurobiologie,FUBerlin,K˛nigin-Luise-Str.
28/30,D-14195Berlin,Germany
EdwardS.Brodkin UniversityofPennsylvaniaSchoolofMedicine,Centerfor
NeurobiologyandBehavior,415CurieBoulevard,Room111,Philadelphia,
PA19104-6140,USA
IanCraig POBox82,SGDPResearchCentre,InstituteofPsychiatry,
DeCrespignyPark,DenmarkHill,LondonSE58AF,UK
CatherineDulac DepartmentofMolecularandCellularBiology,
HarvardUniversity,16DivinityAvenue,Cambridge,MA02138,USA
CraigFerris DepartmentofPsychiatry,UniversityofMassachusettsMedical
School,55LakeAvenueNorth,Worcester,Massachusetts01655,USA
StephenGammie 1117WestJohnsonSt,ZoologyResearchBuilding,
Room213,DepartmentofZoology,UniversityofWisconsin,Madison,
WI 53706,USA
RobertHinde StJohn’sCollege,CambridgeCB21TP,UK
BarryKeverne Sub-DepartmentofAnimalBehaviour,Universityof
Cambridge,HighStreet,Madingley,CambridgeCB38AA,UK
JaapKoolhaas DepartmentofAnimalPhysiology,UniversityofGroningen,
P.O.Box14,9750AAHaren,TheNetherlands
vii
viii PARTICIPANTS
Klaus-PeterLesch KlinikundPoliklinikfˇrPsychiatrieundPsychotherapie,
Universit(cid:1)tWˇrzburg,D-97080Wˇrzburg,Germany
RobinLovell-Badge TheNationalInstituteforMedicalResearch,
TheRidgeway,MillHill,LondonNW71AA,UK
StephenManuck BehavioralPhysiologyLaboratory,Departmentof
Psychology,UniversityofPittsburgh,506OldEngineeringHall,Pittsburgh,
PA15260,USA
ManuelaMartinez DepartmentofPsychobiology,FacultyofPsychology,
UniversityofValencia,Avda.BlascoIba•ez21,46010,Valencia,Spain
RandyNelson DepartmentsofPsychologyandNeuroscience,09Townshend
Hall,TheOhioStateUniversity,Columbus,OH 43210,USA
BerendOlivier DepartmentofPsychopharmacology,UtrechtInstitutefor
PharmaceuticalSciences,UtrechtUniversity,Sorbonnelaan16,3584CA,
Utrecht,TheNetherlands
DonaldPfa¡ (Chair) NeurobiologyandBehavior,TheRockefellerUniversity,
Box275,1230YorkAvenue,NewYork,NY10021-6399,USA
DianeM.Robins DepartmentofHumanGenetics,UniversityofMichigan,
4909Buhl,1241E.CatherineSt,AnnArbor,MI48109-0618,USA
DavidSkuse BehaviouralandBrainSciencesUnit,InstituteofChildHealth,
30GuilfordStreet,LondonWC1N1EH,UK
StephenSuomi NationalInstituteofChildHealthandHumanDevelopment,
31CenterDrive,Bethesda,MD20892,USA
BrianTrainor(NovartisFoundationBursar) BauerCenterforGenomicsResearch,
HarvardUniversity,7DivinityAvenue,Cambridge,MA02138,USA
Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268, Volume 268.
Edited by Gregory Bock and Jamie Goode
Copyright  Novartis Foundation 2005. ISBN: 0-470-01068-1
Introduction
DonaldPfa¡
Neurobiology and Behavior, The Rockefeller University, Box 275, 1230 York Avenue,
NewYork,NY10021-6399,USA
In this introduction I’d like to state some questions that might deserve
consideration during this meeting. To try to do so in a comprehensive way
would be presumptuous of me. So I have, o¡ the top of my head, listed some
back of the envelope questions that might put some of our discussions in a
historical context, and then I will ask Robert Hinde, Barry Keverne and Randy
Nelsontoaddconsiderationsthattheymighthave.
My¢rstquestionmightbetitled‘Beyondtranscription’.Certainly,withrespect
toandrogenice¡ectsonaggressivebehaviours,upuntilnowithasbeeneasiestto
ascribe regulatory in£uences of hormones to transcriptional changes. This was
naturalforaneurobiologisttodobecausethechemistryofDNAissimplerthan
thatofmostothercellularcompounds.Until1944,whenDNAwasdiscoveredto
be the genetic substance, it was considered to be a stupid molecule(cid:1)much too
stupidtocarrythegeneticinformation.Somyquestionis,towhatextentcanwe
envisionfacingthedi⁄cultiesofdealingwithRNAeditingandproteinchemistry
in neurons as part of the business of life, with respect to molecular mechanisms
underlyingaggression?
Second,howarewegoingtoanalysetheindirectaswellasthedirectin£uenceof
genomic changes on aggressive behaviours? In 1941, working with Neurospora,
Beadle and Tatum came up with data that supported the one gene/one enzyme
concept. I would argue that up until a few years ago, the one gene one enzyme
concept dominated functional genomics, but with respect to sex behaviours
whereweknowanawfullot,Ihavebeenabletoarguethatwearealwaysdealing
with patterns of gene expression governing patterns of sociosexual behaviours.
Howdoweapplythiskindofthinkingtoaggression?
Finally, ethology is the science of behaviour. I for one aspire to the kind of
precisionandlawfulnessthatwe¢ndinthephysicalsciences.Towhatextentdo
the stereopathies of aggressive behaviour, and their obvious biological
adaptiveness(atleastinanimals),provideoneofthebestsubjectsforustoprove
thatbehaviouralsciencecanachievethesamekindoflawfulnessandprecisionas
thephysicalsciences?I’llnowaskRobertHindewhathopesorwarningshemight
haveforus.
1
2 PFAFF
Hinde:Iamamis¢tatthismeetingbecauseIhaven’tworkedbelowtheskinfor
40years,letaloneatthemolecularlevel.ButIamoftheopinionthatviolenceis
perhapsthemostimportantproblemhumansface.WhatIwillbelookingforisthe
following.Arewemakingacleardistinctionbetweenaggression(whichisusually
in human studies de¢ned as the intentional a¥iction of harm on another
individual), and aggressiveness (the propensity to be aggressive). One is an act,
the other is a general propensity. Second, are we making a clear distinction
betweenthevarioustypesofaggression?Theseincludeinstrumentalorfelonious
aggression, teasing aggression, revenge aggression and socially acceptable
aggression that is condoned in a gang or small group but not in the general
population, and so on. This approximates to what Donald Pfa¡ calls the ‘form’
of aggression, when he makes the distinction between testosterone-instigated
and maternal aggression. During the papers I shall be thinking of whether it is
the motor pattern that is being studied (and some of the subjects are chosen
because of the stereotyped nature of mouse aggression which makes it easy to
score)orisitthepropensitytouseviolencewithanysortofmotivation,orisit
motivationbeingstudiedinaparticularcontext.
Keverne:Wehaveabroadaudiencehereofresearchersstudyingsubjectsranging
from£iestohumans.Thereisnodoubtthatmanyofthesamegenescrossallof
thesebiologicalgroups.Itisimportanttobearinmindthatwiththecloningand
sequencing of the human and mouse genome, we now know that both have
approximately the same number of genes. Actually, humans have slightly fewer
than the mouse, and the ones we lack are primarily in the olfactory system. We
also know that there is 96% sequence synteny. Clearly, these similar genes and
sequences are building very di¡erent phenotypes. It is important for us to take
intoaccounthowdi¡erentthesephenotypesare,particularlywithrespecttothe
brain and brain development. One of the things that is di¡erent between the
human brain and the small rodent brain is that our behaviour is not primarily
directed by olfactory cues. Secondly, most of the development in our brains
occursinthepostnatalenvironment,anditoccursatatimewhenwearelearning
thesocialcuesofhowtocontrolandregulateourbehaviour.Evolutionarily,this
developmentofthebrainisnotinsigni¢cantwhenwetrytotransferinformation
fromwhatisknowninthe£yormousetothehuman.Atthetranscriptionallevelof
agivengeneitisgoingtoberemarkablysimilar,butintermsofwhatthegenomeis
doing in building a phenotype, it is going to be di¡erent, and in terms of what
humanscandowiththatphenotypeisalsoverydi¡erent.Forexample,muchof
human behaviour is to some extent emancipated from hormonal in£uences.
Women do not need to have undertaken pregnancy and parturition to be good
mothers. We don’t wait until we get the hunger signals from hormones before
wefeed.Wedoourforaginginasupermarketinadvanceofhunger.Aggression
isevenmorecomplexbecauseitinvariablyneedsacontext.Itisrarelyspontaneous