Silva R C B, Gárgaro Ana Carolina, Brandão M L
Laboratório de Psicobiologia, FFCLRP, Campus USP, Av. Bandeirantes 3900, Ribeirão Preto 14049-901, SP, Brazil.
Behav Brain Res. 2004 May 5;151(1-2):93-101. doi: 10.1016/j.bbr.2003.08.015.
It has previously been shown that the median raphe nucleus (MR) is one of the main sources of projections to the septum and hippocampus. 5-HT projections from this nucleus to the hippocampus are implicated in the acquisition and expression of contextual fear (background stimuli), as assessed by freezing. It has also been reported that amygdala is involved in the acquisition of conditioned fear to foreground cues such as light, used as CS. As the MR projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to contextual and classical fear conditioning remains to be elucidated. The present study examined the involvement of the MR serotonergic mechanisms in the expression of two distinct types of conditioned fear responses: contextual freezing and fear conditioning to explicit cue (light) measured in a fear-potentiated startle (FPS) procedure. Animals received MR electrolytic lesions of or microinjections of 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino tetralin) (1 microg/0.2 microl) into the MR, 1 or 7 days after two consecutive training sessions in which they received 10 pairings of the CS (light, 4 s)-US (foot-shocks 0.6 mA, 1s) and were tested in a contextual fear paradigm and in a FPS procedure. The startle was clearly potentiated in the presence of light-CS in animals bearing lesions of or microinjected with 8-OH-DPAT into MR at 1 or 7 days post-training. However, animals bearing MR electrolytic lesions or microinjections of 8-OH-DPAT into the MR at 1 day, but not at 7 days post-training, showed a significant decrease in time spent in freezing than control ones. Thus, the memory for contextual conditioned fear seems to be formed during a time-window shorter than 1 week. As FPS may be produced in lesioned rats unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, the production of contextual freezing and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN.
先前的研究表明，中缝正中核（MR）是向隔区和海马体投射的主要来源之一。该核向海马体的5-羟色胺（5-HT）投射与情境恐惧（背景刺激）的习得和表现有关，通过僵住反应来评估。也有报道称，杏仁核参与对诸如光等前景线索的条件性恐惧的习得，光用作条件刺激（CS）。由于中缝正中核向海马体和杏仁核投射，该中缝核在情境恐惧条件反射和经典恐惧条件反射中的作用仍有待阐明。本研究考察了中缝正中核5-羟色胺能机制在两种不同类型的条件性恐惧反应表现中的作用：情境僵住反应以及在恐惧增强惊吓（FPS）程序中测量的对明确线索（光）的恐惧条件反射。在连续两次训练 sessions 后1天或7天，动物接受中缝正中核的电解损伤或向中缝正中核微量注射8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT，1微克/0.2微升），训练中它们接受10次条件刺激（光，4秒）-非条件刺激（足部电击0.6毫安，1秒）配对，并在情境恐惧范式和FPS程序中进行测试。在训练后1天或7天，接受中缝正中核损伤或向中缝正中核注射8-OH-DPAT的动物，在光条件刺激出现时惊吓明显增强。然而，训练后1天而非7天接受中缝正中核电解损伤或向中缝正中核注射8-OH-DPAT的动物，与对照组相比，僵住时间显著减少。因此，情境条件性恐惧的记忆似乎在短于1周的时间窗口内形成。由于在无法对恐惧情境刺激产生僵住反应的损伤大鼠中可能出现FPS，在每种情况下似乎招募了不同的系统。因此，情境僵住反应和恐惧增强惊吓的产生由中缝正中核不同的5-羟色胺介导回路传递。
