Lucas L R, Celen Z, Tamashiro K L K, Blanchard R J, Blanchard D C, Markham C, Sakai R R, McEwen B S
Laboratory of Endocrinology, Box 165, 1230 York Avenue, Rockefeller University, New York, NY 10021, USA.
Neuroscience. 2004;124(2):449-57. doi: 10.1016/j.neuroscience.2003.12.009.
The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic-pituitary-adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS + NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS + NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.
可见洞穴系统（VBS）是一种慢性社会应激范式，在此范式中，与雌性大鼠同居的雄性大鼠之间会形成优势等级制度。VBS中的雄性大鼠会经历行为和生理变化，这些变化被认为是慢性社会应激的表现。由于尚不清楚慢性社会应激是否会影响动机和奖赏行为，因此对与这些区域相关的脑区进行了检查。通过将大鼠单次（一个VBS饲养和恢复周期）或反复（三个周期）暴露于VBS，研究了单次或反复暴露于VBS对中脑边缘亚区的长期影响。观察VBS中的行为，并将大鼠分为优势者或从属者。从属者根据对急性应激源（即束缚应激）的应激激素（皮质酮）反应进一步细分。正常反应者被归类为应激反应性从属者（SRS），下丘脑-垂体-肾上腺轴反应迟钝的动物被指定为无反应性从属者（NRS）。对照雄性大鼠在VBS期间与一只雌性大鼠配对饲养，恢复期间单独饲养。与对照组相比，SRS单次暴露于VBS以及两个从属组（即SRS + NRS）反复暴露于VBS后，伏隔核（Acb）中的脑啡肽mRNA水平均降低。与对照组相比，NRS单次暴露于VBS后，背外侧尾状壳核（DLCPu）中多巴胺转运体密度降低，NRS反复暴露于VBS后，Acb中多巴胺转运体密度降低。两个从属组（SRS + NRS）单次暴露于VBS后，Acb中多巴胺D2受体密度升高，NRS反复暴露于VBS后，DLCPu、背内侧CPu和Acb中多巴胺D2受体密度升高。在任何组中均未观察到多巴胺D1受体结合的变化。这些结果表明，反复暴露于慢性社会应激后，中脑边缘结构中多巴胺活性的长期变化持续存在，这可能为抑郁症及其随后与药物滥用易感性的共病的神经化学基础提供见解。
