Christianson John P, Paul Evan D, Irani Myra, Thompson Brittany M, Kubala Kenneth H, Yirmiya Raz, Watkins Linda R, Maier Steven F
Department of Psychology and Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
Behav Brain Res. 2008 Nov 3;193(1):87-93. doi: 10.1016/j.bbr.2008.04.024. Epub 2008 May 4.
Research investigating how control over stressors affects behavior often utilizes freezing and shuttle escape learning as the behavioral endpoints. These endpoints have been argued to reflect anxious or depressed states, but these descriptions are problematic. The present study sought to determine the impact of stressor controllability and the dorsal raphé nucleus (DRN) on sucrose preference and juvenile social exploration, putative measures of anhedonia and anxiety that are commonly used in studies of stress per se. In Experiment 1 rats were exposed to escapable stress (ES) or yoked-inescapable stress (IS) tailshocks. In Experiment 2 ES or IS was given 7 days before all rats received IS. In Experiment 3 the DRN was inactivated during IS by microinjection of 8-OH-DPAT. Sucrose preference and social exploration were tested for several days after stress. A fourth experiment confirmed that juvenile social exploration is sensitive to traditional beta-carboline and benzodiazepine manipulations. Both ES and IS reduced sucrose preference, but only IS reduced social exploration. Prior treatment with ES prevented the effect of IS on social exploration but did not prevent the effect of IS on sucrose preference and inactivation of the DRN prevented the effect of IS on social exploration but did not change sucrose preference. The present results indicate that social exploration but not sucrose preference is sensitive to prior stressor controllability, and that DRN activation mediates the effect of IS on social exploration. We argue that DRN-5-HT activation mediates a state of generalized anxiety produced by uncontrollable stress and that juvenile social exploration is a useful behavioral endpoint in stressor controllability studies.
研究应激源控制如何影响行为的实验通常将僵住反应和穿梭箱逃避学习作为行为终点。有人认为这些终点反映了焦虑或抑郁状态,但这些描述存在问题。本研究旨在确定应激源可控性和中缝背核(DRN)对蔗糖偏好和幼年社交探索的影响,蔗糖偏好和幼年社交探索是在应激本身的研究中常用的快感缺失和焦虑的假定指标。在实验1中,大鼠接受可逃避应激(ES)或束缚不可逃避应激(IS)电击。在实验2中,所有大鼠在接受IS电击前7天先接受ES或IS电击。在实验3中,通过微量注射8-OH-DPAT使DRN在IS电击期间失活。在应激后数天测试蔗糖偏好和社交探索。第四个实验证实幼年社交探索对传统β-咔啉和苯二氮䓬类药物处理敏感。ES和IS均降低了蔗糖偏好,但只有IS降低了社交探索。预先给予ES可防止IS对社交探索的影响,但不能防止IS对蔗糖偏好的影响,DRN失活可防止IS对社交探索的影响,但不会改变蔗糖偏好。目前的结果表明,社交探索而非蔗糖偏好对应激源的预先可控性敏感,并且DRN激活介导了IS对社交探索的影响。我们认为DRN-5-羟色胺激活介导了由不可控应激产生的广泛性焦虑状态,并且幼年社交探索是应激源可控性研究中一个有用的行为终点。