Mutlu Oguz, Páleníček Tomáš, Pinterová Nikola, Šíchová Klára, Horáček Jiří, Holubová Kristina, Höschl Cyril, Stuchlík Aleš, Erden Faruk, Valeš Karel
National Institute of Mental Health, Topolova 748, Klecany, 250 67, Czech Republic.
Pharmacology Department, Kocaeli University Medical Faculty, Kocaeli, 41380, Turkey.
Fundam Clin Pharmacol. 2018 Dec;32(6):589-602. doi: 10.1111/fcp.12386. Epub 2018 Jun 27.
The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), Pht-HrTH (2 mg/kg), MK-801 (0.15 mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1 mg/kg), Lia-AKH (1 mg/kg), Pht-HrTH (1 mg/kg), MK-801 (0.1 mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), and Pht-HrTH (2 mg/kg) reversed MK-801 (0.15 mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1 mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1 mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.
脂肪动素和红色素浓缩激素（AKH/RPCH）肽家族控制昆虫的脂肪、碳水化合物和蛋白质代谢。在我们之前的研究中，我们表明AKH具有抗抑郁、抗焦虑和镇痛作用，可引起运动亢进，并在小鼠中发挥神经保护作用并增加脑神经营养因子。本研究的目的是在主动异源位置回避试验（AAPA）中研究帝王大蜻蜓AKH（Ani-AKH）、金环蜻蜓AKH（Lia-AKH）和黑腹果蝇高海藻糖血症激素（Pht-HrTH）对MK-801诱导的记忆衰退的影响，以及在预脉冲抑制试验（PPI）中对MK-801诱导的感觉运动门控缺陷的影响。在AAPA任务中，将长 Evans 大鼠用Ani-AKH（2mg/kg）、Lia-AKH（2mg/kg）、Pht-HrTH（2mg/kg）、MK-801（0.15mg/kg）以及MK-801与这些激素的组合进行亚慢性处理。在预脉冲抑制试验中，在试验前将Wistar白化大鼠用Ani-AKH（1mg/kg）、Lia-AKH（1mg/kg）、Pht-HrTH（1mg/kg）、MK-801（0.1mg/kg）或MK-801与激素的组合进行急性处理。在我们的研究中，Ani-AKH（2mg/kg）、Lia-AKH（2mg/kg）和Pht-HrTH（2mg/kg）逆转了MK-801（0.15mg/kg）在AAPA任务中诱导的认知记忆损害作用。Lia-AKH（1mg/kg）显著增强了MK-801诱导的PPI破坏，而Ani-AKH（1mg/kg）部分增强了MK-801引起的损害，并且Pht-HrTH未改变MK-801的作用。总之，在精神分裂症模型的PPI试验中，AKH对感觉运动门控缺陷没有影响，而在MK-801精神分裂症模型中AKH改善了记忆。
