Age-related decline in water maze learning and memory in rats: strain differences

Abstract

Rats display an age-related impairment in learning and memory; however, few studies have systematically examined this relationship in multiple strains. The present study used a repeated acquisition water maze task to test the hypothesis that age-related decreases in learning and memory occur at different rates in three strains of rats, i.e. Sprague–Dawley (SD), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats. All three strains of rats displayed age-related decreases in spatial learning and memory; however, the rate of decline differed between the strains. Compared to young rats of the same strain, only SHR were significantly impaired at 12 months of age. All three strains displayed moderate impairment in learning the task at 18 months of age, and at 24 months of age all three strains of rats were severely impaired in the task, but SD performed best at 18 and 24 months of age. Further, SD and SHR displayed a probe trial bias at 3 months of age, but only SD had a bias at 12 months of age and none of the rats showed the bias at later ages. Thus, in these three strains, age-related impairment of spatial memory proceeds at different rates.

Introduction

Several lines of evidence suggest that learning and memory gradually decline with advancing age in humans, e.g. [1], [2] and that this age-related impairment extends to spatial learning and memory tasks [9], [18], [29], [30], [33], [39]. These age-related spatial learning and memory deficits have been attributed, in part, to alterations in the connections and function of hippocampal formation [7], [35]. Rats display similar age-related disturbances in the hippocampal formation connectivity and in spatial memory, and therefore, many researchers have employed spatial memory deficits in aged rats as a model of the cognitive deficits associated with aging in humans (e.g. [12], [15]). Compared to spatial memory tasks, other memory tasks do not show as great of an age-related decline. For instance, object recognition does not show an age-related decline [5]. Thus, several studies indicate that age-related impairments in spatial tasks may precede general learning and memory deficits.

Spontaneously hypertensive rats (SHR) are the most frequently used animal model of hypertension, and they have provided important insights into the consequences of the disease on many organ systems [27]. We have previously demonstrated that 12- (compared to the 4-) month-old SHR display a marked deficit in acquisition of an 8-arm radial maze task [41]. In contrast, Sprague–Dawley rats (SD) display no age-related decline in this task until 20 to 24 months of age [41]. Thus, in comparison to SD, SHR display an earlier onset of memory disorders. Chronic antihypertensive treatment of SHR almost completely abolishes the age-related memory decline in 12-month-old SHR [41]. Although learning deficits have also been reported in other hypertensive rodent models of hypertension, including genetic (e.g. [19]) and induced (e.g. [33]) models, the interpretation of these deficits is complicated because the hypertensive models including SHR are different from control normotensive rats in many respects, e.g. SHR are hyper-reactive and hyperactive [17], [18], and hypertension, by itself, is not sufficient to induce the age-related changes in behavior [17]. Thus, although some lines of evidence suggest that hypertension may accelerate or even precipitate memory disorders especially in otherwise compromised animals, other factors also contribute to learning and memory impairments in these rats. In the present study, SHR, genetically related but normotensive Wistar Kyoto rats (WKY), and SD were tested in a water maze task at four different ages to test the hypothesis that each of these three strains of rats display a distinct decline in spatial learning.

Many past studies of age related learning and memory has relied on tasks that are relatively simple even for older rats to perform. In the present study, we employ a repeated acquisition task in the water maze [19], [38]. In this task, a hidden platform remains in the same position for four consecutive trials on a single day. The following day, the position of the platform is moved to a new, randomly assigned position. This method provides a relatively difficult task that is extremely sensitive to impairments in spatial learning [10], and information on both working and reference memory can be extracted from the data. This task facilitates the differentiation of age-related changes in learning and memory at intermediate ages, i.e. between very young and very old animals [6], [10].

The results of the present studies demonstrate that there are strain-related differences in the rate of decline in this spatial learning and memory task. In young rats there are also strain-related differences in learning and memory.