Flügge G, Ahrens O, Fuchs E
German Primate Center, Department of Neurobiology, Kellnerweg 4, D-37077 Göttingen, Germany.
Cell Tissue Res. 1997 Apr;288(1):1-10. doi: 10.1007/s004410050787.
The prefrontal cortex has been reported to be involved in the regulation of emotional behaviour by integrating cognitive, emotional and autonomic information processes, and impairments of its functions are implicated in psychopathologies such as depression. Neuronal functioning in the prefrontal cortex is under the control of the noradrenergic and the serotonergic system which are both activated during stress. The present study aimed to quantify the effect of chronic psychosocial stress on alpha2-adrenoceptors, beta-adrenoceptors, and serotonin1A receptors in the prefrontal cortex. Male tree shrews (Tupaia belangeri) were subjected to subordination stress for 2, 10, 21 and 28 days, and binding sites for the alpha2-adrenergic antagonists 3H-rauwolscine and 3H-RX821002, for the beta-adrenergic antagonist 125I-iodocyanopindolol, and for the 5-hydroxytryptamine (5HT)1A receptor agonist 3H-8-hydroxy-2-(di-n-propylamino)tetralin were quantified by in vitro receptor autoradiography. Chronic psychosocial stress induced time-dependent receptor down- and upregulations. Beta-adrenoceptors were transiently reduced in numbers after just 2 days of psychosocial stress which is interpreted as agonist-mediated downregulation induced by high local concentrations of noradrenaline released from terminals originating from the locus coeruleus. Alpha2-adrenoceptors were transiently downregulated after 10 days, and upregulated after 28 days of psychosocial stress. These data indicate that the noradrenergic system adapts to the stress by counterbalancing its receptor numbers. 5HT1A receptors were only downregulated after 28 days of psychosocial stress, and thus react later than the noradrenergic receptors. In summary, our results show that monoaminergic receptors in the prefrontal cortex of tree shrews undergo dynamic changes during chronic psychosocial stress. These alterations probably have an impact on neuronal activity, and might contribute to the behavioural changes which have been previously described in subordinate male tree shrews.
据报道,前额叶皮质通过整合认知、情感和自主神经信息过程参与情绪行为的调节,其功能受损与抑郁症等精神病理学有关。前额叶皮质中的神经元功能受去甲肾上腺素能和血清素能系统的控制,这两个系统在应激过程中均被激活。本研究旨在量化慢性心理社会应激对前额叶皮质中α2-肾上腺素能受体、β-肾上腺素能受体和5-羟色胺1A受体的影响。雄性树鼩(Tupaia belangeri)接受2、10、21和28天的从属应激,通过体外受体放射自显影法定量α2-肾上腺素能拮抗剂3H-萝芙辛和3H-RX821002、β-肾上腺素能拮抗剂125I-碘氰吲哚洛尔以及5-羟色胺(5HT)1A受体激动剂3H-8-羟基-2-(二正丙基氨基)四氢萘的结合位点。慢性心理社会应激诱导了时间依赖性的受体下调和上调。心理社会应激仅2天后,β-肾上腺素能受体数量短暂减少,这被解释为由蓝斑核释放的去甲肾上腺素终末局部高浓度诱导的激动剂介导的下调。心理社会应激10天后,α2-肾上腺素能受体短暂下调,28天后上调。这些数据表明,去甲肾上腺素能系统通过平衡其受体数量来适应应激。5HT1A受体仅在心理社会应激28天后下调,因此比去甲肾上腺素能受体反应更晚。总之,我们的结果表明,树鼩前额叶皮质中的单胺能受体在慢性心理社会应激期间经历动态变化。这些改变可能会影响神经元活动,并可能导致先前在从属雄性树鼩中描述的行为变化。