137. Chronic EPI-inositol is anxiolytic in the plus maze model in rats

Thursday Abstracts ghrcocorticoidactionsrue mediatedmostlyby membraneevents which interferewith the activityof other ceil-surfacereceptors,while chrmdc steroideffects involvegenomicregulationof proteinsynthesisthrough intracellularreceptors. Supportedby the FatherSean O’SullivanResearchCentre,St. Joseph’s Hospital BIOLPSYCHIATRY 1998;43:1S-133S 41s pharmacologiceffects. Effects of the treatmentsthemselveswere observed only shortly after drug treatment, with fluoxetine acting to increaseACTHin the treatedand mother-rearedgroup,and DMf acting to decrease ACTH in both treated groups. The results support the influence of primate mothers on developmentof psychobiological systemsin their infants. 135. EXPERIMENTAL ASTHMA IN A GENETIC ANIMAL MODEL OF DEPRESSION 137. CHRONIC EPI-INOSITOL IS ANXIOLYTIC IN THE PLUS MAZE MODEL IN RATS V.J. Djuricl, D.H. Overstreet2, A. Dragomirl, L. Smithl, G. COX1& M. Steinerl H. Einatl, Z. Elkabez-Schwartzl, H. Cohenl, O. Kofman2 & R.H. Belmakerl ‘FatherSean O’SullivanResearchCerrtre,St. Joseph’sHospitaL McMasterUniversityL8N 4A6 Hamilton,Ontario,Canada;2 Skipper BowlesCenterfor AlcoholStudies,Universityof NorthCarolina, Cha@ Hill, NC 27599-7178 Ministryof HealthMentalHealthCenter, IFacukyof HealthSciences and ‘Departmentof BehavioralSciencesBen GurionUniversityof the Negev,Bee.rsheva,Israel Several empirical studies have reported high prevalence of atopic disordersin Woplewithdepression.In, addition,hyperrqxmsivenessto choiinergicagonists has been found both in people diagnosedwith allergicasthmaand in peoplediagnosedwith depression.In this study, cholinergic hyperresponsiveFlinders Sensitive Line (FSL) rata (an animal model of depression),and their control counterpartsFlinders Resistant Line (FRL) rats were compared for their susceptibilityto experimentalasthma.Airwayresponsivenesswas assessedin spontaneouslybreathing,unrestrainedanimalsby meansof wholebodyplethysmography.Increasedairwayresponsivenessof FSLrats was evidenced as a morepronouncedincreasein Perdrvalue(enhancedpause,an index of bronchoconstriction) across differentconcentrationsof methacholine (F.,ll, = 10.27;p< O.001).In subsequentexperirnen%FSLandFRLrats weresensitizedto ovalbuminandchallengedwithnebulizedantigen.The data indicate that geneticallytransmittedcholinergichyperresponsiveness of the FSL rat is paralleled by its increased susceptibilityto allergen-inducedbronchoconstriction(Fl,3.r = 54.86; p<O.~1) and inflammationof the airways (FI,34= 15.65; p< O.001).‘flus study provides further evidence for a common cholinergicmechanismin susceptibilityto both asthmaand depression. Sponsoredby St. Joseph’sHealthCareFoundationandOntarioThoracic Society 136. REARING CONDITION AND HPA AXIS RESPONSE TO FLUOXETINE AND DMI IN MONKEYS A.S. Clarkel, G.W. Kraeme~, W.T. McKinneyl & D.J. Kupfer3 myo-Inositolis a simpleisomerof ghrcosethatservesas theprecursorfor the phospholipidphosphoinositolbiphosphate(PI) cyclefromwhichthe second messengers Inositol-3-phosphate(IP3) and Di-Acyl-Glycerol (DAG)are derived. In humans,myo-inositolhasbeenreportedto havetherapeuticefficacyin patients with obsessivecompulsivedisorder (Fux et al., 1996),panic disorder(Benjaminet al., 1995),and depression(Levineet al., 1995). Behavioraleffects of myo-inositolhave been demonstratedin animal modelsof psychiatricdisordersincludingthe plusmazemodelof anxiety (Cohenet al., 1997).These effects of myo-inositolwere thoughtto be consequencesof its beinga substratefor theenzymephosphatidylinositol (PI) synthase. epi-fnositolis anartificialstereoisomerofmyo-inositol thatisnota substrate for PI synthaae.Althoughpreviouslyconsideredinactivein biological systems(BenjamirrandAgranoff,1969),recentfindingsindicatethatit may haveat leastonebehavioraleffectthatis similarto the oneof myo-inositol, aa it wasdemonstratedto attenuateMhium-pilocarpine inducedseizuresas does myc-inositol(Ritishiet al., 1996;WilliamsarrdJope, 1995).The presentstudymeasuredthebehaviorof ratsin an elevatedplusmazemodel of anxietyafterchrotic treatmentof 11 dailyip injectionsof epi-inositol, myn-inositol, or controlsolution.Epi-inositolreducedaoxietylevelsof rats comparedwithcontrols,anditseffectwasstrongertharrthatofmyo-inositol. ‘l%eincreasedrelativeeffectof epi-inositoicouldbe due to slowermetabolismor to differentmechanismof action. 138. EFFECTS OF DOPAMINE D4 ANTAGONISTS ON MNEMONIC ACTIVITY OF NEURONS IN PRIMATE PREFRONTAL CORTEX IDepsrtmentof Psychiatry,NorthwesternUniversityMedicalSchool, ‘Universityof Wisconsin-Madison,3Universityof PittsburghSchooIof Medicine G.V. Williams, S.G. Rae, H-C. Leung & P.S. Goldman-Rakic Normal hypothalamic-pituitary-adrenal (HPA) axis activity has been widelyreportedto be alteredas a result of early experiencein rodents. Here the effectsof early socirdexperienceon later responseof the HPA axis to separationsand pharmacologictreatmentswere examinedin 36 rhesusmonkeys.HPAaxis activitywas measuredin mother-rearedand peer-rearedmonkeyinfantsin conjunctionwith six repeatedseparations from and reunionswith their cagemates.Withinrearinggroups,infants were assignedto one of threetreatmentgroupsthat receivedwith either fluoxetirre(2 mg/kg),desipramirre(DMI,5 mg/lrg)or placebo(saline). Mother-rearedmonkeysshowedsigniticarrtlyhigherACTHand cortisol levels over multiple samples than peer-reared animals in spite of Sectionof Neurobiology,Yale UniversitySchoolof Medicine,New Haven,CT 06510 As part of our ongoinginvestigationof the modulationof the cellular basisof workingmemoryby dopamine,we haveexaminedthe effectsof the selectiveD4 antagonists,includingU101958and L745870,on the activityof prefrontalcortical neuronsin monkeysperforminga spatial oculomotordelayed-responsetask. Delayactivitywas increasedin 33% of both cell types, suggestinga significantpresenceof the receptoron bothchases of neuron.However,delayactivitywas alsoreducedin 21% in bothcell types,indicatingan augmentationof localinhibitorycircuits.