111. Preservation of adenylyl cyclase activity and 5-HT 1A receptor-G protein coupling in the human brain postmortem

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BIOLPSYCHIATRY 1998;43:1S-133S

Thursday Abstracts

centrrd nucleus of amygdala(CN)and supraoptic nucleus(SON)of extrshypothalsrnicsites in rat brainsat one week,two week,four week, eight week intervalsafter Imipramine(IMI),a prototypesntidepressanq administration.Theresultsare as follows;In PVN,no significantchange of CRHrnRNAexpressionwas detectedat one week after IMl administration,but increasesof CRHrnRNAexpressionwere detectedat two weeka,four weeks,eight weeks after IMI admirristnition(p
subsequently moreaemtomn “ reuptakethanthe short(S)allele.‘he biologicalmeasuresof expressionandtirnctionof the S/Sandthe US genotypes aresirrrikmTranspoti-facilitateduptakeof serotorrinmaybe a susceptibility factorfor suicidaIbebaviour.This studyexaminedthe associationof suicidalbebaviourin Chinesepatientswith DSM IV schizophreniaand polymorphism in theregulatoryregionof the5HlT gene.Allelicpolymorphismsofthe5J-llTgenewasdetermimdbyP(2Rgenotypingin60suicidal and 53 non-suicidrdpatientswith schizophreniaof Han Chinesedescent. Tbercwasa small(3%)excessin h proportionof theS genotype(S/Sand LAS) inthesuicideattempters(92%)ascomparedtothoaewithoutsuicidally (89%). However,the corresponding95% confidenceinterval for this differencerangedfrom-8%to 14%whichdoesnotexcludethe possibility of noexcess.Themaultssuggestthepossibilityof, at mos~onlya margimd effectof the 5HTTgeneas a susceptibilityfactorfor suicidalbehsviourin scbimplrrenia.

111. PRESERVATION OF ADENYLYL CYCLASE ACTIVITY AND 5-HT 1A RECEPTOR-G PROTEIN COUPLING IN THE HUMAN BRAIN POSTMORTEM

113. NEUROLEPTIC DRUG EFFECTS ON SYNAPTOPHYSIN GENE EXPRESSION LEVELS

D. Marazziti, A. Giromella, R.M. Mazzoni, G. Giannaccini & L. Palego Instituteof Psychiatry,Universityof Pis4 via Roma67, 1-56100Pisa, Italy Thepostmortemstabilityof adenylylcyclaseactivityandof the serotonin (5-HT)receptor-Gproteincouplingwere evaluatedin some regionsof the humanand rat brains.As the 5-HTIAreceptorhas bear reportedto be negativelycoupledto adenylylcyclase,the inhibitoryeffect of 5-HT and 8-OH-DPATon forskolin-stimulatedadenylylcyclaseactivitywas also determined.Adenylylcyclsse activitywas detectablein both basal and forskolin-stimulatedconditionsfor 48 hourspostmortemin the rat brain and in all human brain regions examined (prefrontal cortex, hipprrcsmpusand dorsal rspbe). 5-HT and 8-OH-DPATinhibitedforskolin-stimulatedadenylylcyclsse activityin a dose-dependentmanner for48 hoursafterdeathin therat andhumanbrain.A regionalityof 5-HT and 8-OH-DPATpotenciesand efficacieswas also observedin human tissues: 5-HT was more potent in the cortex and in the bippocsmpus; 8-OH-DPATpotencywas greaterin dorsatraphe.The 5-HTIAreceptor antagonist(+)WAY 100135was able to shift 8-OH-DPATpotenciesin all humanareas. Such findingsindicatethat 5-HT-sensitiveadenylyl-cyclaseactivity is resistantto postmortemdegradationand can be furthercharacterizedin humanbrain tissues.

112. SUICIDALITY AND SEROTONIN TRANSPORTER GENE POLYMORPHISM S.A. Chon 1’5, A.H.N, Ta 2, W.L. Leea, D. Machin$ , A.O.M. Chan ? & L.L. Ng5 *ClsrkeInstituteof Psychiatry,Toronto,Canada;21nstituteof Molcculwand Cell Biology,Singapore;~rm TockSengHospital, Singapore;4NatiorratMedicalResearchCouncil,Singapore; ‘WoodbndgeHospital,Singapore Abnormrditiesof semtonmsynthesisand metabolkmis aasasiatedwith suicidahty.A genepotentiallyimportmtin controllingserotoninmetabolism istheserotordntransporter(5HT17gene.Oneoftheallele-softhetmmpmta gene (calledL for long allele) containsa 44 amino-acidinsertionin a r%@s@Yregionof the genewhichhas greatertfanacdptionalactivityand

E.H. Harnidl, S.M. Baca2, G.E. Meredith3, T.M. Hydel & M.F. Eganl INeuropsychiatricResearchHospital,IRP, NIMH,Washington,DC 20032;2Departmentof Neuroscience,EmoryUniversity,Atlanta,GA 30322;3Departmentof Neurology,The RoyalCollegeof Surgeons, Dublin2, Ireland Theuseof neurolepticdrugsis commonin thetreatmentof schizophrenia and related psychoses.One of the possiblemechanismsof neuroleptic drug action is to alter synaptic density in different brain regions, especiallythosereceivingheavydopsrrdnergicimervation (P. J. Hsrrisou AntipsychoticDrugs and their Side Effects, Academic Press, London,99-110,1993).To furtherexplorethe natureof this process,we studiedthe effectof bothshort-termandlong-termhaloperidoltreatment and withdrawalon the levels of synaptophysingene expression.It has been demonstratedthat the quantitationof synaptophysinmRNAlevels can be a suitable mwker of synaptic density in post-mortembrain samples(S. L. Eastwood,et. al., Neuroscience,59, 881-892,1994).In this report,we emphasizethe shorttermeffectsof haloperidoltreatment for 3 and 21 days with or withoutwithdrawalfor 24 hours(n=6 for all groups)on the synaptophysinrnRNAlevels in the medialaspectof the nucleussccurnbensshell in rats. Usingin situ hybridizationbistochemistry, we detected a significant (p
114. D3 AGONIST NEUROLEPTIC (PRANHPEXOLER) IMPROVES SET-SHIFT AND REWARD EFFECT M. Lyonl, C.N. Karson2 & A.B. Whiteheadl wiversity of Arkansmfor MedicalSciences,LittleRock AR72203; AR 72205 2JotmL. McClelkurMemorialVeteranaHospital,LittleROCIG Tested D3 agonist neurolcptic(PratnipexoleR)onfetal developmental model of negativesymptomsehizopbrenia(Lyonand McClure, 1994;