Rambousek Lukas, Palenicek Tomas, Vales Karel, Stuchlik Ales
Institute of Physiology, Academy of Sciences of the Czech Republic , Prague , Czech Republic.
Prague Psychiatric Center , Prague , Czech Republic.
Front Behav Neurosci. 2014 May 16;8:180. doi: 10.3389/fnbeh.2014.00180. eCollection 2014.
The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior, and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval, and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention, and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg disrupted reinforced retrieval in the MWM. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.
血清素系统在精神分裂症病理生理学中的作用已通过致幻剂实验得以阐明。将致幻剂应用于人体会导致感知、认知、情绪的变化，并诱发类似精神分裂症症状的类精神病症状。在啮齿动物研究中，急性给予致幻剂会影响感觉运动门控、运动活动、社交行为以及包括工作记忆在内的认知，这些表型被视为精神分裂症的动物模型。人类认知的复杂性和独特性引发了关于利用5-HT2A受体激动剂的动物模型有效性的问题。因此，本研究调查了赛洛西宾对大鼠记忆获取、强化检索和记忆巩固的影响。赛洛西宾是裸盖菇素的主要代谢产物，作为5-HT2A受体的激动剂，同时5-HT2C和5-HT1A受体也有参与。首先，我们测试了赛洛西宾对旋转迷宫记忆获取的影响，旋转迷宫是一项需要利用远端线索导航、注意力和认知协调的空间任务。赛洛西宾在两个剂量（1和4毫克/千克）下均显著损害了旋转迷宫的记忆获取。即使在额外的实验环节中大鼠只接受生理盐水，较高剂量的赛洛西宾也会阻碍学习过程。接下来，我们研究了赛洛西宾对莫里斯水迷宫（MWM）强化检索和巩固的影响。4毫克/千克的剂量破坏了MWM中的强化检索。然而，较低剂量的应用没有任何显著影响。最后，训练后注射的低剂量和高剂量赛洛西宾均未导致MWM中记忆巩固出现缺陷。综上所述，赛洛西宾剂量依赖性地损害了旋转迷宫的记忆获取和MWM中的强化检索；然而，它对记忆巩固没有影响。
