Reis Fernanda L V, Masson Sueli, de Oliveira Amanda R, Brandão Marcus L
Laboratório de Psicobiologia, Departamento de Psicologia, FFCLRP-USP, Campus, Av Bandeirantes, 3900, 14049-901 Ribeirão Preto, Brasil.
Pharmacol Biochem Behav. 2004 Oct;79(2):359-65. doi: 10.1016/j.pbb.2004.08.006.
The involvement of dopaminergic mechanisms in fear and anxiety is still unclear. Behavioral studies aimed to disclose the involvement of dopamine in anxiety have reported anxiolytic-like, anxiogenic-like and lack of effects with the use of dopaminergic agonists and antagonists in animal models of anxiety. This work was an attempt to contribute to this field by providing evidence that these discrepancies may be due to the kind of aversive situation the animals experience in these models. The present study examined the effects of a dopaminergic agonist apomorphine, a dopaminergic D(1) antagonist SCH 23390 and a D(2) receptor antagonist sulpiride on the two-way avoidance response test (CAR) and on the switch-off responses to light (SOR). In both tests, learning was assessed by the performance of the animals across four blocks of 10 trials in which light was paired to footshocks (CAR) or only light was presented to the animals (SOR). The obtained data show that rats learn to make a shuttling response to avoid the shock in the CAR test and maintain a regular pace of switch-off responses in the SOR. While sulpiride and SCH 23390 administrations prevented learning of the avoidance responses, apomorphine injections produced a dose-dependent enhancement in the conditioned learning in the CAR test. The number of escape responses was unchanged by these drugs. In the light-induced switch-off test, apomorphine reduced the number of switch-off responses whereas sulpiride increased these responses. These findings suggest that the involvement of dopaminergic mechanisms in threatening situations depends on the nature of the aversive stimulus. Activation of D(1) and D(2) receptors seems to be implicated in the heightened aversiveness to conditioned stressful situations, as assessed by the CAR test. Thus, blockade of D(1) and D(2) receptors may be necessary for attenuating the aversiveness triggered by these conditioned fear stimuli. In contrast, mechanisms mediated by D(2) receptors seem to be involved in the setting up of adaptive responses to innate fear reactions. Therefore, the signal of the modulatory dopaminergic mechanisms on defensive behavior will depend on the type of emotional stimuli triggering the coping reaction.
多巴胺能机制在恐惧和焦虑中的作用仍不清楚。旨在揭示多巴胺在焦虑中作用的行为学研究报告称,在焦虑动物模型中使用多巴胺能激动剂和拮抗剂后,出现了抗焦虑样、促焦虑样以及无作用等不同结果。这项工作试图通过提供证据表明这些差异可能归因于动物在这些模型中所经历的厌恶情境类型,从而为该领域做出贡献。本研究考察了多巴胺能激动剂阿扑吗啡、多巴胺D(1)拮抗剂SCH 23390和D(2)受体拮抗剂舒必利对双向回避反应测试(CAR)以及对光关闭反应(SOR)的影响。在这两项测试中,通过动物在四个包含10次试验的组块中的表现来评估学习情况,其中在CAR测试中,光与足部电击配对,而在SOR测试中仅向动物呈现光。获得的数据表明,大鼠在CAR测试中学会做出穿梭反应以避免电击,并在SOR测试中保持规律的关闭反应节奏。虽然舒必利和SCH 23390的给药阻止了回避反应的学习,但阿扑吗啡注射在CAR测试中产生了剂量依赖性的条件性学习增强。这些药物对逃避反应的数量没有影响。在光诱导的关闭测试中,阿扑吗啡减少了关闭反应的数量,而舒必利增加了这些反应。这些发现表明,多巴胺能机制在威胁情境中的作用取决于厌恶刺激的性质。通过CAR测试评估,D(1)和D(2)受体的激活似乎与对条件性应激情境的增强厌恶有关。因此,阻断D(1)和D(2)受体可能是减轻这些条件性恐惧刺激引发的厌恶感所必需的。相比之下,由D(2)受体介导的机制似乎参与了对先天恐惧反应的适应性反应的建立。因此,多巴胺能调节机制对防御行为的信号将取决于触发应对反应的情绪刺激类型。