Diabetic type II Goto-Kakizaki rats show progressively decreasing exploratory activity and learning impairments in fixed and progressive ratios of a lever-press task.

摘要

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.