prenatal iv cocaine: mri evidence of ventricular enlargement in adult offspring
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in the central noradrenergic (NE) system, the integrity of theASR was examined following Idazoxan (IDZ, an a 2-adrenergic receptor antagonist). Virgin Long-Evans female rats,implanted with an IV access port prior to breeding, wereadministered saline, 0.5, 1.0, or 3.0 mg/kg of cocaine HCL(COC) from GD8-21 (lx/day-GD8-14, 2x/day-GDl5-21).At -120 days of age, 1 M and 1 F from each litter received0.5 mg/kg IDZ immediately prior to evaluation of the ASR(San Diego Instruments, 100 dB(A) white noise stimulus,70dB(A) background, 10 min adaptation, 36 trials, and 10sec ITI). The peak amplitude of the ASR following IDZadministration was significantly enhanced in saline controls;this effect was significantly reduced as a linear function ofprenatal cocaine dose and was not affected by the offspring'ssex. These data suggest an alteration in the descending NEsystem. Given our prior evidence of greater sensitivity to theattention impairing effect of IDZ (Bayer et aI., '96),suggesting an alteration in ascending NE function, the locuscoeruleus may be a primary target for prenatal cocaine.
(Support: DA09160, DA07559, DAl1337 & ES06259)
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MACTUTUS, c.r., R.M. BOOZE, M. ZHANG, M.A.NICHOLLS, A.H. ANDERSEN, M.A. WELCH, B.l.STRUPP, AND c.r. AVISON, Div. Pharmacal. Exp.Therap., ColI. of Pharmacy/THRl, Dept. Anat. & Neurobiol.and MRISC, Call. of Medicine, Univ. of Kentucky,Lexington, KY and Dept. Psychology, Cornell University,Ithaca, NY. Prenatal IV cocaine: MRI evidence ofventricular enlargement in adult offspring.
Application of noninvasive imaging techniques to infantsof mothers exposed to cocaine in utero provides evidence ofcerebral vascular hemorrhage and ventricular enlargement in-10% of the cases (Dixon & Bejar, '89). Given initialserendipitous observations with MRI techniques, weexamined the effects of prenatal cocaine on the cerebralventricles. Artifactual compression (freezing) or expansion(perfusion) compromises ventricle size measurement withstandard anatomical techniques. Virgin Long-Evans femalerats, implanted with an IV access port prior to breeding,were administered saline, 0.5, 1.0, or 3.0 mg/kg or cocaineHCL (COC) from GD8-21 (lx/day-GD8-14, 2x/day-GD1521). At D90-120, male rats from vehicle and 3.0 mg/kgCOC litters (nse S) were anesthetized (urethane), placed in aVarian 4.7T scanner, and a 3-1mm-slice coronal set wasobtained. Ordinal ranking and analysis of three observer's(treatment blind) rankings each confirmed larger ventriclesin the prenatal COC exposed animals (ps<0.04). Forquantitation, each 1 mm slice of the Tl-weighted image setwas interpolated to a final resolution of 300 urn andsegmented from the pixel intensity histogram via an intensityalgorithm. The mean lateral and 3rd ventricle size estimate(rnnr') was 23.7 ± 3.0 (vehicle, outlier of 145 removed) vs.37.5 ± 4.4 (3 mg/kg COC)(F(l,13)::::6.3, p ~ 0.026). Thesedata suggest that 1) ventricle enlargement may be a genuineclinical sequelae of in utero COC exposure, and 2) in vivo
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MRI measurement may permit a priori prediction of whichanimals may be most severely compromised in neurobehavioral or other anatomical measures. (Support: MRISCFund, DA09160, DA07559, DA11337, ES06259, NS35080).
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VORHEES, C.Y., L.L. MORFORD, S.L. INMAN, M.FUKUMURA*, M.S. MORAN* and H.W. BROENING. Div.of Dev. Biology, Children's Hosp. Res. Found. & Univ, ofCincinnati, Cincinnati, OH 45229. EtTects of dose-rate onMorris maze cued and place learning in rats treated with dmethamphetamine (MAlon postnatal (Pl days 11-20.
MA is neurotoxic to adult rats after 4 doses (2-hr. apart).In developing animals, spatial learning deficits arc induced by2 doses/d. given on PII-20. We compared the 4-dose to the 2dose regimen. IS litters of Sprague-Dawley rats were assignedto 3 groups and received 4 doses s.c. at 2-hr. intervals on P 1120. Controls received saline, group MA20 received 20 mg/kgd-MA on the first and fourth doses and saline in between, andgroup MAIO received 10 mg/kg d-MA on all doses. 2M/2Fwere tested/litter beginning on P50. Liller was the wilt ofanalysis and gender was a within factor. Both MA dosesproduced significant reductions in weight gain duringtreatment which gradually recovered. There were no groupdifferences in pre-maze straight channel trials. On cued trials,there was a significant main effect of treatment. Longerlatencies were seen in the MA20 group. On spatial trials,there were significant treatment elTects on latency, cumulativedistance from platform and path length. MA groups navigatedto the platform less efficiently than controls; the MA groupsdid not ditTer from one another. On probe trials, there were nodifferences on platform site crossing, but significant elTectswere seen on percent time in target quadrant and averagedistance from platform; both MA groups were similar anddifferent from controls. No differences were seen on reversal,but on additional reduced platform trials, group wassignificant. Only the MAIO group performed significantlyless efficiently. Analysis of covariance with cued learning asthe covariate for hidden platform performance, revealed thatacquisition and reduced platform dilTerences were notaccounted for by cued platform dilTercnces. The data replicateour previous findings that P 11-20 MA exposure inducesspecific spatial learning and memory impairmcnrs and showedthat dose rate has only a small effect on performance.(Supported by NIH grant DAOG733).
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OHMORI11, H., K. YAMASHITAI)·, T. HArrAl),M. YASUDAl)., T. MICHIKAWAl)., K.KAWAN021 ., H. OGURA21. • K. MIKOSHIBN).,1IDepartment of Anatomy, Hiroshima UniversitySchool of Medicine, 2)Tsukuba ResearchLaboratories, Eisai Co. Ltd., -Department ofNeurobiology, Institute of Medical Science, TheUniversity of Tokyo. .tJ.~urotoxic effects ofE.~en~~iE.on develo~ngmous~rain.