The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study.
The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study.
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DOI：
10.1007/s00213-015-3963-5
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发表时间：
2015-11
影响因子：
3.4
通讯作者：
Robbins TW
中科院分区：
文献类型：
--
作者：
Alsiö J;Nilsson SR;Gastambide F;Wang RA;Dam SA;Mar AC;Tricklebank M;Robbins TW
抑制性学习需要联想学习和执行功能来抑制非适应性反应。在例如精神分裂症和强迫症中观察到反向学习缺陷，并且涉及包括眶额皮质（OFC）的神经回路。血清素能功能与人类和实验动物的视觉逆转学习密切相关，但对哪些受体亚型参与其中知之甚少。本研究的目的是测试全身和内OFC 5-HT 2C受体拮抗作用对大鼠视觉反转学习的影响，并评估这些影响的心理机制在新的触摸屏范例。在实验1-2中，我们使用新的3刺激任务来研究通过SB 242084（0.1、0.5和1.0 mg/kg i. p.）跨站点实验3评估了SB 242084在2-选择反转学习中的作用。在实验4中，我们通过巴氯芬/蝇蕈醇诱导的OFC失活验证了一种适用于神经药理学微量输注的新型触摸屏连续视觉反转任务。在实验5中，我们测试了OFC内SB 242084（1.0或3.0 μg/侧）对该任务中的性能的影响。在实验1-3中，SB 242084减少了早期错误，但增加了晚期错误的标准。在实验5中，内OFC SB 242084减少早期错误，而不增加后期错误的反转范式验证OFC依赖（实验4）。内OFC 5-HT 2C受体拮抗作用降低大鼠新型触摸屏反向学习范式的持续性。全身性5-HT 2C受体拮抗作用还损害了后期学习-一个强大的影响，观察跨网站和潜在的冲动。这些结论进行了讨论的神经机制的基础上的逆转学习和精神疾病的相关性。本文的在线版本（doi：10.1007/s 00213 -015-3963-5）包含补充材料，可供授权用户使用。
Reversal learning requires associative learning and executive functioning to suppress non-adaptive responding. Reversal-learning deficits are observed in e.g. schizophrenia and obsessive-compulsive disorder and implicate neural circuitry including the orbitofrontal cortex (OFC). Serotonergic function has been strongly linked to visual reversal learning in humans and experimental animals but less is known about which receptor subtypes are involved. The objectives of the study were to test the effects of systemic and intra-OFC 5-HT2C-receptor antagonism on visual reversal learning in rats and assess the psychological mechanisms underlying these effects within novel touchscreen paradigms. In experiments 1–2, we used a novel 3-stimulus task to investigate the effects of 5-HT2C-receptor antagonism through SB 242084 (0.1, 0.5 and 1.0 mg/kg i.p.) cross-site. Experiment 3 assessed the effects of SB 242084 in 2-choice reversal learning. In experiment 4, we validated a novel touchscreen serial visual reversal task suitable for neuropharmacological microinfusions by baclofen-/muscimol-induced OFC inactivation. In experiment 5, we tested the effect of intra-OFC SB 242084 (1.0 or 3.0 μg/side) on performance in this task. In experiments 1–3, SB 242084 reduced early errors but increased late errors to criterion. In experiment 5, intra-OFC SB 242084 reduced early errors without increasing late errors in a reversal paradigm validated as OFC dependent (experiment 4). Intra-OFC 5-HT2C-receptor antagonism decreases perseveration in novel touchscreen reversal-learning paradigms for the rat. Systemic 5-HT2C-receptor antagonism additionally impairs late learning—a robust effect observed cross-site and potentially linked to impulsivity. These conclusions are discussed in terms of neural mechanisms underlying reversal learning and their relevance to psychiatric disorders. The online version of this article (doi:10.1007/s00213-015-3963-5) contains supplementary material, which is available to authorized users.