GENETIC-VARIATION IN VULNERABILITY TO THE BEHAVIORAL-EFFECTS OF NEONATAL HIPPOCAMPAL DAMAGE IN RATS

被引:115
作者
LIPSKA, BK
WEINBERGER, DR
机构
[1] Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Washington, DC 20032, 2700 Martin Luther King Avenue, SE
关键词
STRAIN SPECIFICITY; FISCHER; 344; RATS; LEWIS RATS; MESOLIMBIC DOPAMINE SYSTEM; ANIMAL MODEL;
D O I
10.1073/pnas.92.19.8906
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We explored how two independent variables, one genetic (i.e., specific rat strains) and another environmental (i.e., a developmental excitotoxic hippocampal Lesion), contribute to phenotypic variation, Sprague-Dawley (SD), Fischer 344 (F344), and Lewis rats underwent two grades of neonatal excitotoxic damage: small and large ventral hippocampal (SVH and LVH) lesions, Locomotion was tested before puberty [postnatal day 35 (P35)] and after puberty (P56) following exposure to a novel environment or administration of amphetamine, The behavioral effects mere strain-and lesion-specific. As shown previously, SD rats with LVH lesions displayed enhanced spontaneous and amphetamine-induced locomotion as compared with controls at P56, but not at P35. SVH lesions in SD rats had no effect at any age, In F344 rats with LVH lesions, enhanced spontaneous and amphetamine-induced locomotion appeared early (P35) and was exaggerated at P56, SVH lesions in F344 rats resulted in a pattern of effects analogous to LVH lesions in SD rats-i.e., postpubertal onset of hyperlocomotion (P56), In Lewis rats, LVH lesions had no significant effect on novelty- or amphetamine-induced locomotion at any age, These data show that the degree of genetic predisposition and the extent of early induced hippocampal defect contribute to the particular pattern of behavioral outcome, These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia, a disorder characterized by phenotypic heterogeneity, genetic predisposition, a developmental hippocampal abnormality, and vulnerability to environmental stress.
引用
收藏
页码:8906 / 8910
页数:5
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