Peterschmitt Y, Meyer F, Louilot A
INSERM U 666 and Institute of Physiology, Louis Pasteur University, Faculty of Medicine, 11 rue Humann, 67085 Strasbourg Cedex, France.
Neuroscience. 2008 Jun 26;154(3):898-910. doi: 10.1016/j.neuroscience.2008.03.073. Epub 2008 Apr 7.
It has previously been reported that dopamine (DA) responses observed in the core and dorsomedial shell parts of the nucleus accumbens (Nacc) in latent inhibition (LI) are dependent on the left entorhinal cortex (ENT). The present study was designed to investigate the influence of the left ventral subiculum (SUB) closely linked to the ENT on the DA responses obtained in the Nacc during LI, using an aversive conditioned olfactory paradigm and in vivo voltammetry in freely moving rats. In the first (pre-exposure) session, functional blockade of the left SUB was achieved by local microinjection of tetrodotoxin (TTX). In the second session, rats were aversively conditioned to banana odor, the conditional stimulus (CS). In the retention (test) session the results were as follows: (1) pre-exposed (PE) conditioned animals microinjected with TTX, displayed aversion toward the CS; (2) in the core part of the Nacc, for PE-TTX-conditioned rats as for non-pre-exposed (NPE) conditioned animals, DA levels remained close to the baseline whereas DA variations in both groups were significantly different from the DA increases observed in PE-conditioned rats microinjected with the solvent (phosphate-buffered saline (PBS)); (3) in the shell part of the Nacc, for PE-TTX-conditioned rats, DA variations were close to or above the baseline. They were situated between the rapid DA increases observed in NPE-conditioned animals and the transient DA decreases obtained in PE-PBS-conditioned animals. These findings suggest that, in parallel to the left ENT, the left SUB controls DA LI-related responses in the Nacc. The present data may also offer new insight into the pathophysiology of schizophrenia.
此前有报道称,在潜伏抑制(LI)过程中,伏隔核(Nacc)核心和背内侧壳部分观察到的多巴胺(DA)反应依赖于左侧内嗅皮质(ENT)。本研究旨在利用厌恶条件性嗅觉范式和自由活动大鼠体内伏安法,研究与ENT紧密相连的左侧腹侧下托(SUB)对LI期间Nacc中获得的DA反应的影响。在第一个(预暴露)阶段,通过局部微量注射河豚毒素(TTX)实现对左侧SUB的功能阻断。在第二个阶段,对大鼠进行香蕉气味(条件刺激,CS)的厌恶条件训练。在保留(测试)阶段,结果如下:(1)预先暴露(PE)并经TTX微量注射的条件动物对CS表现出厌恶;(2)在Nacc的核心部分,对于PE-TTX条件大鼠和未预先暴露(NPE)的条件动物,DA水平保持接近基线,而两组中的DA变化与注射溶剂(磷酸盐缓冲盐水(PBS))的PE条件大鼠中观察到的DA增加显著不同;(3)在Nacc的壳部分,对于PE-TTX条件大鼠,DA变化接近或高于基线。它们介于NPE条件动物中观察到的快速DA增加和PE-PBS条件动物中获得的短暂DA减少之间。这些发现表明,与左侧ENT并行,左侧SUB控制Nacc中与DA-LI相关的反应。目前的数据也可能为精神分裂症的病理生理学提供新的见解。