Bratt A M, Kelley S P, Knowles J P, Barrett J, Davis K, Davis M, Mittleman G
Department of Psychology, The University of Memphis, TN 38152, USA.
Psychoneuroendocrinology. 2001 Feb;26(2):121-45. doi: 10.1016/s0306-4530(00)00033-0.
Mature rats were given lesions of the hippocampus (HIPPO), subiculum (SUBIC) or fimbria-fornix (FIFO) and then received the mild chronic stressors of food deprivation and isolation housing for ten months prior to testing. Group differences in circadian activity were investigated along with locomotion elicited by amphetamine (AMP 1.0-2.0 mg/kg i.p.) alone, and following the corticosterone (CORT) synthesis inhibitor, metyrapone (MET 10.0-25.0 mg/kg i.p.). Basal levels of plasma CORT, (ng/ml), plasma glucose (GLUC, mmol/l), thymic and splenic wet weights were subsequently determined along with complete blood counts (CBC). In comparison to age matched, unoperated controls, selective SUBIC lesions altered the circadian periodicity of locomotion, while rats with FIFO lesions were spontaneously hyperactive. Both HIPPO and FIFO animals showed significantly higher levels of amphetamine-induced locomotion. In all groups metyrapone significantly enhanced locomotion elicited by amphetamine, probably due to a pharmacokinetic interaction between these drugs. In comparison to controls, animals in the HIPPO group showed significant reductions in plasma glucose levels, decreased thymic wet weights and reductions in lymphocyte numbers, indicating lesion-related immuno-suppression. These findings highlight a functional difference among the effects of these specific hippocampal lesions on neural regulation of the HPA axis, under conditions of chronic mild stress, suggesting that the modulatory influence of the hippocampus on the stress axis is dependent on the neuroanatomical location and total extent of cell loss within this structure. They further suggest that the heightened response to amphetamine occurs independently of any lesion-induced changes in modulation of the HPA axis.
成年大鼠接受海马体（HIPPO）、下托（SUBIC）或穹窿海马伞（FIFO）损伤，然后在测试前十个月接受食物剥夺和单独饲养这两种轻度慢性应激源。研究了昼夜活动的组间差异，以及单独使用苯丙胺（AMP 1.0 - 2.0 mg/kg腹腔注射）引发的运动，以及在给予皮质酮（CORT）合成抑制剂美替拉酮（MET 10.0 - 25.0 mg/kg腹腔注射）后的运动情况。随后测定了血浆CORT的基础水平（ng/ml）、血浆葡萄糖（GLUC，mmol/l）、胸腺和脾脏湿重以及全血细胞计数（CBC）。与年龄匹配的未手术对照组相比，选择性SUBIC损伤改变了运动的昼夜节律，而FIFO损伤的大鼠表现出自发性多动。HIPPO和FIFO组的动物在苯丙胺诱导的运动方面均表现出显著更高的水平。在所有组中，美替拉酮均显著增强了苯丙胺引发的运动，这可能是由于这些药物之间的药代动力学相互作用。与对照组相比，HIPPO组的动物血浆葡萄糖水平显著降低，胸腺湿重减少，淋巴细胞数量减少，表明存在与损伤相关的免疫抑制。这些发现突出了在慢性轻度应激条件下，这些特定海马体损伤对HPA轴神经调节作用的功能差异，表明海马体对应激轴的调节影响取决于该结构内神经解剖位置和细胞损失的总体程度。它们还进一步表明，对苯丙胺的增强反应独立于HPA轴调节中任何由损伤引起的变化而发生。
