Higley J D, Suomi S J, Linnoila M
Laboratory of Clinical Studies, DICBR, NIAAA, Bethesda, MD.
Biol Psychiatry. 1992 Jul 15;32(2):127-45. doi: 10.1016/0006-3223(92)90016-s.
Twenty-two rhesus macaques were studied longitudinally from infancy to early adolescence in order to assess the effects of developmental change, experimental history, gender, and individual variation on the response of the catecholaminergic, serotonergic, and adrenocortical systems to separation-induced stress. Experimental effects were assessed by comparing subjects reared for the first 6 months of life either with their mothers or in peer groups. Developmental changes in response to repeated separation stress were assessed by subjecting the monkeys to four sequential 4-day social separations when they were 6 and 18 months old. At both ages, prior to, and on the last day of the first and fourth separations, cerebrospinal fluid (CSF) was obtained from the cisterna magna to assess monoamine metabolite concentrations, and blood samples were collected to assess plasma cortisol concentrations. Blood samples were also obtained on the first day of each separation at each age. Age-related declines were found in both homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations for all subjects. Social separation consistently increased CSF 3-methoxy-4-hydroxyphenolglycol (MHPG) over baseline levels, but decreased HVA concentrations, whereas 5-HIAA levels increased following the first, but not the fourth separation. Plasma cortisol increased rapidly immediately after separation and remained higher than baseline on day 4 of both the first and fourth separation. Independent of age and experimental condition, peer-rearing increased CSF MHPG and plasma cortisol concentrations. During year 1, peer-rearing also produced diminished CSF 5-HIAA concentrations in female monkeys relative to female mother-reared monkeys, but increased male peer-reared monkeys' concentrations relative to mother-reared males. Interindividual differences were highly stable, with significant correlations both within and between years for each of the three metabolites and cortisol.
对22只恒河猴从婴儿期到青春期早期进行了纵向研究，以评估发育变化、实验经历、性别和个体差异对儿茶酚胺能、血清素能和肾上腺皮质系统对分离诱导应激反应的影响。通过比较在生命的前6个月与母亲一起饲养或在同龄群体中饲养的受试者来评估实验效果。通过在猴子6个月和18个月大时对它们进行连续4次为期4天的社会分离，来评估对反复分离应激的发育变化。在两个年龄段，在第一次和第四次分离之前以及最后一天，从枕大池获取脑脊液（CSF）以评估单胺代谢物浓度，并采集血样以评估血浆皮质醇浓度。在每个年龄段每次分离的第一天也采集血样。发现所有受试者的高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）浓度均随年龄下降。社会分离始终使脑脊液3-甲氧基-4-羟基苯乙二醇（MHPG）高于基线水平，但降低了HVA浓度，而5-HIAA水平在第一次分离后升高，但在第四次分离后没有升高。分离后血浆皮质醇立即迅速升高，并且在第一次和第四次分离的第4天均高于基线水平。与年龄和实验条件无关，同龄饲养增加了脑脊液MHPG和血浆皮质醇浓度。在第1年期间，同龄饲养还使雌性猴子的脑脊液5-HIAA浓度相对于由母亲饲养的雌性猴子有所降低，但相对于由母亲饲养的雄性猴子，同龄饲养的雄性猴子的浓度有所增加。个体间差异高度稳定，三种代谢物和皮质醇在各年内和各年之间均具有显著相关性。
