Avanzi V, Brandão M L
Laboratório de Psicobiologia, FFCLRP, Campus USP, Av. Bandeirantes 3900, 14049-901, Ribeirão Preto, SP, Brazil.
Behav Brain Res. 2001 Nov 29;126(1-2):175-84. doi: 10.1016/s0166-4328(01)00254-6.
We have shown that the median raphe nucleus (MRN) is involved in the control of contextual fear conditioning. Also, electrolytic lesion in the MRN causes signs of behavioral disinhibition, with an increase in locomotor activity measured in an open field. In this work, we have extended this study by analyzing the behavioral and autonomic responses in a contextual conditioning paradigm in rats with either neurochemical lesions from N-methyl-D-aspartate (NMDA), or microinjected with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the MRN. The animals received NMDA, 8-OH-DPAT or saline microinjections into the MRN before the conditioning experiments, during which they were subjected to ten conditioning trials in an experimental chamber (same context) where they received foot-shocks (0.7 mA, 1 s with 20 s intervals). The next day, the animals were tested again either in the same or in a different experimental chamber, where the duration of freezing, number of rearings, bouts of micturition and number of fecal boli were recorded. Control rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly inhibited in rats with NMDA lesions or with 8-OH-DPAT microinjections into the MRN. These MRN manipulations also produced a reduction in micturition. Such effects were context-specific since 8-OH-DPAT in MRN did not affect fear conditioned responses to tone previously associated with foot-shocks. In the open-field test, rats with neurotoxic lesions or with 8-OH-DPAT microinjections into the MRN had higher horizontal locomotor activity than control rats, without the number of rearings changing. As rats injected with 8-OH-DPAT into the MRN may freeze to a tone in a conditioned test paradigm and also show increased activity in an open field test the functional role of MRN on locomotor activity and contextual fear conditioning are clearly dissociated. Altogether, these results clearly show that such 5-HT mechanisms of the MRN serve as a neural substrate for the storage process of the context fear.
我们已经表明中缝正中核（MRN）参与情境恐惧条件反射的控制。此外，MRN的电解损伤会导致行为去抑制的迹象，在旷场中测量的运动活动增加。在这项工作中，我们通过分析在具有来自N-甲基-D-天冬氨酸（NMDA）的神经化学损伤或在MRN中微量注射8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）的大鼠的情境条件反射范式中的行为和自主反应，扩展了这项研究。在条件反射实验之前，动物接受了向MRN内微量注射NMDA、8-OH-DPAT或生理盐水处理，在此期间，它们在一个实验箱（相同情境）中接受了十次条件反射试验，在那里它们接受足部电击（0.7 mA，持续1 s，间隔20 s）。第二天，动物在相同或不同的实验箱中再次接受测试，记录僵住持续时间、站立次数、排尿次数和粪便颗粒数。置于同一箱中的对照大鼠比暴露于不同情境的大鼠表现出更多的僵住行为。在具有NMDA损伤或向MRN中微量注射8-OH-DPAT的大鼠中，这种僵住行为明显受到抑制。这些对MRN的操作还导致排尿减少。由于MRN中的8-OH-DPAT不影响对先前与足部电击相关的音调的恐惧条件反射反应，因此这些效应具有情境特异性。在旷场试验中，具有神经毒性损伤或向MRN中微量注射8-OH-DPAT的大鼠比对照大鼠具有更高的水平运动活动，而站立次数没有变化。由于向MRN中注射8-OH-DPAT的大鼠在条件反射测试范式中可能会对音调产生僵住反应，并且在旷场试验中也表现出活动增加，因此MRN对运动活动和情境恐惧条件反射的功能作用明显不同。总之，这些结果清楚地表明，MRN的这种5-羟色胺机制作为情境恐惧储存过程的神经基础。
