232. - Stress — Restress: An animal model of HPA abnormalities in PTSD

Abstract

s mOL PSYCIIIATRY 1996;39;500-666 567 binding. Theantisense treatment withCRH.-R AS-DON when :Jpplicll to clonal mouse pituitary cells reduced CRH·clicitcd ACTH release. Moreover, chronic infusion of CRH1R AS·DON into the central nucleus of the amygdala reduced anxiety-related behavior. This effect. however. wasnotassociated with reductions ofCRH1·R mRNA and CRH binding in this particular bruin area, Similar Investigations using AS-OON targeted against theCRH2R mRNA failed to induceanxiolytic effects in rats thal were rendered anxious by exposure to social defeat. These findings support the idea that the CRH, receptor plays it key role in mcdlating CRH·etici{ed anxiety and thus is II prime target for anxiolytlc drugs. 232. STRESS RESTRESS: AN ANIMAL MODEL OF HPA ABNORMALITIES IN PTSD I. Liberzon, M, Krstov, & E.A. Young MHRI, University of Michigan. Ann Arbor, MI 48104 While ACTH andcorticosterone responses have been extensively studied in normal or chronically stressed animals, little is known regarding the longer lasting effects of a single severe stressoron this system. This is pilrticularly important since II single stressful event can result in post traumatic stress disorder in humans. Specific HPA axis abnorrnalltiesr low 24h glucocorticoid secretion and hypersensitive negative feedback were reported in this disorder. In the current study we examined the effects of delayed stress on corticosterone and ACTH responses to restrcss and on ghicocerticold negative feedback sensitivity in rats, Sprague-Dawley male rots (250 g) were studied in II stress restress paradigm in two experiments. with and without pretreatment with cortisol. After single severe stress (2 hours restrain + swim + ether), anima/ 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing ::111 {he autosomes at an average marker density of 14 eM. Over 110.000 genotypes have been generated on the whole set of families (as of November 1995)and the data have been analyzed under both dominant and a recessive models. No 100 scores exceed 2.0 foreithermodel. Two markers give lod scoresover 1.0 under dominant model, and live under the recessive model. Under the homogeneous dominant genetic model wehave 100 scoresbelow-2.0 for greaterthan85% of the genetic length of the autosomes, This collection of pedigrees is lessinformative under therecessive model. Consequently, less than 50% of 'he genetic length of the autosomes have lod scores below -2.0 with the homogeneous recessive model. Given the lack of significant positive lad scores and the presence of lod scoresbelow ·2.0 for almost all of the autosomes, we conclude' that panic disorder is unlikely to be caused by a single dominant genetic locus. A single recessive locus. dominant or recessive loci with genetic heterogeneity, ami multiple additive genetic loci can not be excluded from our results. 234. A TRAIT MARKER FOR PANIC DISORDER