Vandresen-Filho Samuel, França Lucas Moreira, Alcantara-Junior José, Nogueira Lucas Caixeta, de Brito Thiago Marques, Lopes Lousã, Junior Fernando Mesquita, Vanzeler Maria Luzinete, Bertoldo Daniela Bohn, Dias Paula Gomes, Colla André R S, Hoeller Alexandre, Duzzioni Marcelo, Rodrigues Ana Lúcia S, de Lima Thereza C M, Tasca Carla Inês, Viola Giordano Gubert
Programa de Pós-graduação em Neurociências, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, Brazil; Departamento de Ciências Básicas em Saúde, Universidade Federal de Mato Grosso, Boa Esperança, Cuiabá, MT, Brazil.
Departamento de Ciências Básicas em Saúde, Universidade Federal de Mato Grosso, Boa Esperança, Cuiabá, MT, Brazil.
Physiol Behav. 2015 May 1;143:27-34. doi: 10.1016/j.physbeh.2015.02.024. Epub 2015 Feb 17.
Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby inhibiting cell synthesis of cholesterol and isoprenoids. Moreover, several studies have been evaluating pleiotropic effects of statins, mainly because they present neuroprotective effects in various pathological conditions. However, knowledge about behavioral effects of statins per se is relatively scarce. Considering these facts, we aimed to analyze behavioral responses of atorvastatin or simvastatin-treated mice in the open field test, elevated plus maze and object location test. Atorvastatin treatment for 7 consecutive days at 1 mg/kg or 10 mg/kg (v.o.) or simvastatin 10 mg/kg or 20 mg/kg enhanced cognitive performance in object location test when compared to control group (saline-treated mice). Simvastatin effects on mice performance in the object location test was abolished by post-training infusion of the beta-adrenoceptor antagonist propranolol. Atorvastatin and simvastatin did not change the behavioral response in open field and elevated plus-maze (EPM) tests in any of the used doses. These data demonstrate the positive effects of both statins in cognitive processes in mice, without any alteration in locomotor parameters in the open field test or anxiolytic-like behavior in EPM. In conclusion, we demonstrate that atorvastatin and simvastatin per se improve the cognitive performance in a rodent model of spatial memory and this effect is related to beta-adrenergic receptors modulation.
他汀类药物是3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的抑制剂，从而抑制细胞内胆固醇和类异戊二烯的合成。此外，多项研究一直在评估他汀类药物的多效性，主要是因为它们在各种病理条件下具有神经保护作用。然而，关于他汀类药物本身行为效应的知识相对较少。考虑到这些事实，我们旨在分析阿托伐他汀或辛伐他汀处理的小鼠在旷场试验、高架十字迷宫和物体位置试验中的行为反应。与对照组（生理盐水处理的小鼠）相比，连续7天以1mg/kg或10mg/kg（口服）给予阿托伐他汀或10mg/kg或20mg/kg给予辛伐他汀可提高物体位置试验中的认知表现。训练后注射β-肾上腺素能受体拮抗剂普萘洛尔可消除辛伐他汀对小鼠物体位置试验表现的影响。阿托伐他汀和辛伐他汀在任何使用剂量下均未改变旷场试验和高架十字迷宫（EPM）试验中的行为反应。这些数据表明两种他汀类药物对小鼠认知过程均有积极作用，在旷场试验中对运动参数无任何改变，在EPM中也无类似抗焦虑行为。总之，我们证明阿托伐他汀和辛伐他汀本身可改善啮齿动物空间记忆模型中的认知表现，且这种作用与β-肾上腺素能受体调节有关。
