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通过僵住行为和恐惧增强惊吓反应评估中度和高度情境性恐惧的药理学解离

Pharmacological dissociation of moderate and high contextual fear as assessed by freezing behavior and fear-potentiated startle.

作者信息

Santos Julia Maria, Gárgaro Ana Carolina, Oliveira Amanda Ribeiro, Masson Sueli, Brandão Marcus Lira

机构信息

Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP 14040-901, Brazil.

出版信息

Eur Neuropsychopharmacol. 2005 Mar;15(2):239-46. doi: 10.1016/j.euroneuro.2004.10.004.

Abstract

The amplitude of the whole-body acoustic startle response is reliably enhanced when elicited in the presence of foreground signals, such as light, previously paired with footshocks. It has been shown that this enhancement is evident by moderate fear levels, but is less affected by high fear levels. Potentiation of the acoustic startle reflex has also been reported in the presence of background cues previously associated with footshocks. However, the effects of anxiolytic drugs on different levels of fear elicited by moderate and intense contextual fear conditioning associated with startle reflex have not been examined yet. To approach this issue, we examined the effects of the anxiolytic, midazolam, on two intensities of contextual fear; freezing behavior and the startle response to loud noise. First, we compared the magnitude of the freezing behavior and the startle amplitude during the testing sessions in groups of rats submitted to fear conditioning using 0.3 and 0.6 mA as unconditioned stimuli (10 stimuli of 1 s each, intertrial interval from 60 to 180 s). Afterwards, the effects of midazolam (0.5 and 1.0 mg/kg) were assessed in these two conditions. Rats showed a potentiated startle reflex and a significant freezing behavior to moderate fear conditioning, which were both attenuated by midazolam. Higher levels of fear conditioning caused more intense freezing behavior without enhancing the startle reflex. Whereas midazolam reduced this freezing response, the startle response was unaffected. These results are indicative that anxiolytic-sensitive freezing and fear-potentiated startle are triggered by moderate contextual fear conditioning, while contextual conditioning with the use of high footshocks causes a distinct pattern of behavioral responses, which is only partially affected by midazolam. Due to the differential sensitivity to midazolam of these two patterns of startle responses generated as a function of the intensity of contextual fear conditioning, it is proposed that they represent moderate and intense aversive states that may be related to anxiety or panic/phobic conditions, respectively.

摘要

当在存在先前与足部电击配对的前景信号(如光)的情况下引发全身听觉惊吓反应时,其幅度会可靠地增强。研究表明,这种增强在中等恐惧水平时很明显,但受高恐惧水平的影响较小。在存在先前与足部电击相关的背景线索的情况下,也有报道称听觉惊吓反射会增强。然而,抗焦虑药物对与惊吓反射相关的中等强度和强烈情境恐惧条件所引发的不同恐惧水平的影响尚未得到研究。为了解决这个问题,我们研究了抗焦虑药物咪达唑仑对两种强度的情境恐惧的影响;即僵住行为和对巨响的惊吓反应。首先,我们比较了在使用0.3和0.6毫安作为非条件刺激(每次1秒的10次刺激,试验间隔为60至180秒)进行恐惧条件训练的大鼠组测试期间的僵住行为幅度和惊吓幅度。之后,在这两种条件下评估了咪达唑仑(0.5和1.0毫克/千克)的效果。大鼠对中等恐惧条件训练表现出增强的惊吓反射和显著的僵住行为,两者均被咪达唑仑减弱。更高水平的恐惧条件训练导致更强烈的僵住行为,但并未增强惊吓反射。虽然咪达唑仑减少了这种僵住反应,但惊吓反应未受影响。这些结果表明,抗焦虑敏感的僵住和恐惧增强的惊吓是由中等情境恐惧条件训练触发的,而使用高强度足部电击的情境条件训练会导致不同的行为反应模式,仅部分受咪达唑仑影响。由于这两种作为情境恐惧条件训练强度函数产生的惊吓反应模式对咪达唑仑的敏感性不同,因此提出它们分别代表可能与焦虑或惊恐/恐惧状态相关的中等和强烈厌恶状态。

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