Leslie Julian C, Shaw David, McCabe Ciara, Reynolds David S, Dawson Gerard R
School of Psychology, University of Ulster, Shore Road, Newtownabbey BT37 0QB, UK.
Neurosci Biobehav Rev. 2004 May;28(3):229-38. doi: 10.1016/j.neubiorev.2004.01.003.
Extinction following positively reinforced operant conditioning reduces response frequency, at least in part through the aversive or frustrative effects of non-reinforcement. According to J.A. Gray's theory, non-reinforcement activates the behavioural inhibition system which in turn causes anxiety. As predicted, anxiolytic drugs including benzodiazepines affect the operant extinction process. Recent studies have shown that reducing GABA-mediated neurotransmission retards extinction of aversive conditioning. We have shown in a series of studies that anxiolytic compounds that potentiate GABA facilitate extinction of positively reinforced fixed-ratio operant behaviour in C57B1/6 male mice. This effect does not occur in the early stages of extinction, nor is it dependent on cumulative effects of the compound administered. Potentiation of GABA at later stages has the effect of increasing sensitivity to the extinction contingency and facilitates the inhibition of the behaviour that is no longer required. The GABAergic hypnotic, zolpidem, has the same selective effects on operant extinction in this procedure. The effects of zolpidem are not due to sedative action. There is evidence across our series of experiments that different GABA-A subtype receptors are involved in extinction facilitation and anxiolysis. Consequently, this procedure may not be an appropriate model for anxiolytic drug action, but it may be a useful technique for analysing the neural bases of extinction and designing therapeutic interventions in humans where failure to extinguish inappropriate behaviours can lead to pathological conditions such as post-traumatic stress disorder.
在阳性强化的操作性条件反射之后的消退会降低反应频率，至少部分是通过无强化的厌恶或挫折效应实现的。根据J.A.格雷的理论，无强化会激活行为抑制系统，进而引发焦虑。正如所预测的那样，包括苯二氮䓬类药物在内的抗焦虑药物会影响操作性消退过程。最近的研究表明，减少γ-氨基丁酸（GABA）介导的神经传递会延缓厌恶条件反射的消退。我们在一系列研究中表明，增强GABA作用的抗焦虑化合物会促进C57B1/6雄性小鼠中阳性强化的固定比率操作性行为的消退。这种效应在消退的早期阶段不会出现，也不依赖于所给予化合物的累积效应。在后期增强GABA作用具有提高对消退意外情况的敏感性的效果，并有助于抑制不再需要的行为。GABA能催眠药唑吡坦在该过程中对操作性消退具有相同的选择性作用。唑吡坦的作用并非由于镇静作用。我们一系列实验中有证据表明，不同的GABA-A亚型受体参与了消退促进和抗焦虑作用。因此，该程序可能不是抗焦虑药物作用的合适模型，但它可能是一种有用的技术，用于分析消退的神经基础以及设计针对人类的治疗干预措施，在人类中，无法消除不适当行为可能会导致诸如创伤后应激障碍等病理状况。
