Moreira Tiago, Malec Ewa, Ostenson Claes-Göran, Efendic Suad, Liljequist Sture
Department of Clinical Neuroscience, Division of Drug Dependence Research, Building L4a:00, Karolinska Institutet, SE-17176 Stockholm, Sweden.
Behav Brain Res. 2007 Jun 4;180(1):28-41. doi: 10.1016/j.bbr.2007.02.034. Epub 2007 Feb 25.
Learning and memory impairments associated with diabetes have been reproduced in rodent models of diabetes type I, but few studies have been performed in spontaneously type II diabetic rodents. The study of type II diabetic rats such as the Goto-Kakizaki (GK) rat is of advantage when characterizing the development of cognitive impairments specifically caused by the progression of the disease and not by its treatment. We thus hypothesized that GK rats might display learning impairments when compared to non-diabetic Wistar rats. In the present study, we employed a lever-press task, a behavioural paradigm which allows the study of response-reinforcement learning, discrimination of a rewarding lever (using a two-choice positional discrimination task), and the ability to increase operant behaviour when requirements for reward increase (using a progressive ratio [PR]). In parallel, locomotor activity was compared between strains to assess exploratory activity and behavioural habituation to a novel environment. Diabetic GK rats made significantly less lever-presses with increasing fixed ratios and, throughout the sessions, a trend for increased selection errors was observed in these animals. In addition, a significant reduction in the maximum number of lever-presses made by GK rats was observed during the PR sessions. Locomotor activity of GK rats was higher on the first day of exploration but significantly decreased with familiarization to the environment. The present results suggest that the diabetic-like symptomatology in GK rats led to a reduction of exploratory activity and of lever-pressing during fixed and progressive ratio schedules, likely caused by learning impairments.
与糖尿病相关的学习和记忆障碍已在I型糖尿病啮齿动物模型中得到重现,但针对自发性II型糖尿病啮齿动物的研究较少。研究II型糖尿病大鼠,如Goto-Kakizaki(GK)大鼠,在表征由疾病进展而非治疗引起的认知障碍发展时具有优势。因此,我们假设与非糖尿病Wistar大鼠相比,GK大鼠可能表现出学习障碍。在本研究中,我们采用了杠杆按压任务,这是一种行为范式,可用于研究反应强化学习、辨别奖励杠杆(使用二选一位置辨别任务)以及当奖励要求增加时增加操作性行为的能力(使用累进比率[PR])。同时,比较了不同品系之间的运动活动,以评估探索活动和对新环境的行为习惯化。随着固定比率的增加,糖尿病GK大鼠的杠杆按压次数显著减少,并且在整个实验过程中,观察到这些动物的选择错误有增加的趋势。此外,在PR实验中观察到GK大鼠的最大杠杆按压次数显著减少。GK大鼠在探索的第一天运动活动较高,但随着对环境的熟悉而显著降低。目前的结果表明,GK大鼠的糖尿病样症状导致在固定和累进比率实验中探索活动和杠杆按压减少,这可能是由学习障碍引起的。