Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats
Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats
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DOI：
10.1038/sj.npp.1301584
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发表时间：
2008-07-01
影响因子：
7.6
通讯作者：
Robbins, Trevor W.
中科院分区：
文献类型：
--
作者：
Boulougouris, Vasileios;Glennon, Jeffrey C.;Robbins, Trevor W.
5-羟色胺(5-羟色胺，或5-羟色胺)与改变行为的能力密切相关，以应对不断变化的刺激-奖励偶发事件。然而，关于不同的5-羟色胺受体在逆转学习中的作用的信息很少。因此，我们研究了全身应用5-HT2A拮抗剂M100907(0、0.01、0.03和0.1 mg/kg，i.p.)的作用。5-HT2C拮抗剂SB 242084(0、0.1、0.3、1.0 mg/kg，i.p.)关于工具性两水平空间辨别和连续空间反转学习任务的绩效，其中两个水平都存在，并且只有一个水平被强化。要求大鼠在固定比例3的加固计划下对加固杠杆作出反应。在达到标准之后，提出了一系列会议期间的逆转。M100907和SB 242084都没有改变在空间辨别和保留先前加强的意外情况期间的表现。M100907通过增加对标准的试验(仅在最高剂量下)和在反转1中对标准的不正确反应，显著损害了逆转学习，这种行为模式表现为先前增强的杠杆上的持续性反应增加。相反，SB 242084通过减少反转1中的试验次数和对标准的不正确反应来改善反转学习，显著减少了持久性反应。这些数据支持5-HT2A和5-HT2C受体在认知灵活性和反应抑制中具有不同作用的观点。在5-HT2C受体拮抗后观察到的逆转学习能力的改善表明，这些受体可能为一些神经精神障碍的治疗进步提供潜力，这些障碍是认知障碍的一个特征，包括强迫症。
Serotonin (5-hydroxytryptamine, or 5-HT) is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies. However, there is little information on the contribution of different 5-HT receptors in reversal learning. Thus, we investigated the effects of systemic administration of the 5-HT2A antagonist M100907 (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) and the 5-HT2C antagonist SB 242084 (0, 0.1, 0.3, and 1.0 mg/kg, i. p.) on the performance of an instrumental two-lever spatial discrimination and serial spatial reversal learning task, where both levers were presented and only one was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of within-session reversals was presented. Neither M100907 nor SB 242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses to criterion in Reversal 1, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB 242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative responses. These data support the view that 5-HT2A and 5-HT2C receptors have distinct roles in cognitive flexibility and response inhibition. The improved performance in reversal learning observed following 5-HT2C receptor antagonism suggests these receptors may offer the potential for therapeutic advances in a number of neuropsychiatric disorders where cognitive deficits are a feature, including obsessive-compulsive disorder.