Beaudet G, Paizanis E, Zoratto F, Lacivita E, Leopoldo M, Freret T, Laviola G, Boulouard M, Adriani W
INSERM U1075 COMETE UNICAEN, University of Caen Normandie, Caen, F-14000, France.
Istituto Superiore di Sanità, Center for Behavioral Sciences and Mental Health, Rome, I-00161, Italy.
Synapse. 2017 Dec;71(12). doi: 10.1002/syn.21995. Epub 2017 Aug 17.
Gambling disorder is associated to an increased impulsivity, a high level of novelty-seeking and a dysregulation of the forebrain neurotransmission systems. However, the neurobiological mechanisms of this addictive disorder are not fully understood and no valid pharmacological approach has yet been approved. The present study aimed to investigate the effect of 5-HT7 receptor (5-HT R) stimulation with a brain penetrant and selective agonist, LP-211 (0.25 and 0.50 mg kg i.p.) during post-experience consolidation, (i) acutely in a novelty-preference test (Exp. 1) or (ii) sub-chronically in the Probabilistic-Delivery Task (rPDT, commonly used to measure individual differences in risk proneness of rats; Exp. 2). Results of Exp. 1 showed that 5-HT R activation improves consolidation of chamber-shape memory in the novelty-preference test, leading to significant novelty-induced hyperactivity and recognition, in conditions where controls displayed a null-preference. These results suggest that 5-HT Rs may be involved in the consolidation of information inherent to spatial environments, facilitating the recognition of novelty. Furthermore, in the operant rPDT (Exp. 2), 5-HT R activation shifts the choice towards a larger yet unlikely reward and turns the propensity of rats towards risk-prone behavior. Thus, 5-HT Rs stimulation apparently strengthens the consideration of future, bigger rewards, also enhancing the seeking of it by operant pokes. These effects may well be explained by LP-211 actions on hippocampal versus prefrontal cortex-mediated regulations, leading to improved (though suboptimal) strategy formation. However, further experiments are necessary to determine more in depth the serotonergic pathways involved.
赌博障碍与冲动性增加、高度寻求新奇以及前脑神经传递系统失调有关。然而，这种成瘾性障碍的神经生物学机制尚未完全明确，目前尚无有效的药物治疗方法获批。本研究旨在探讨在经历后巩固阶段，使用具有脑渗透性的选择性5-HT7受体（5-HT R）激动剂LP-211（腹腔注射，剂量为0.25和0.50 mg/kg）的效果，（i）在新奇偏好测试中进行急性给药（实验1），或（ii）在概率性投递任务中进行亚慢性给药（rPDT，常用于测量大鼠风险倾向的个体差异；实验2）。实验1结果表明，在对照组表现出无偏好的情况下，5-HT R激活可改善新奇偏好测试中对箱形记忆的巩固，导致显著的新奇诱导的多动和识别。这些结果表明，5-HT R可能参与空间环境固有信息的巩固，促进对新奇事物的识别。此外，在操作性rPDT实验（实验2）中，5-HT R激活使大鼠的选择转向更大但不太可能获得的奖励，并使大鼠倾向于冒险行为。因此，5-HT R刺激显然加强了对未来更大奖励的考量，也通过操作性戳击增强了对它的寻求。这些效应很可能是由LP-211对海马体与前额叶皮质介导的调节作用来解释的，从而导致（尽管并非最优）策略形成得到改善。然而，需要进一步的实验来更深入地确定所涉及的5-羟色胺能途径。
