Effects of stress, corticosterone, and epinephrine administration on learning in place and response tasks

Abstract

These experiments examined the effects of prior stress, corticosterone, or epinephrine on learning in mazes that can be solved efficiently using either place or response strategies. In a repeated stress condition, rats received restraint stress for 6 h/day for 21 days, ending 24 h before food-motivated maze training. In two single stress conditions, rats received a 1-h episode of restraint stress ending 30 min or 24 h prior to training. Single stress ending 30 min prior to training resulted in a significant interaction of stress and learning on the two tasks, with significant enhancement of learning in the response task and non-significant impairment in the place task. Neither acute nor chronic stress significantly altered learning in either task when the stress ended 24 h before training. Thus, the anterograde effects of stress on maze learning ended within a single day. Two stress-related hormones, corticosterone and epinephrine, were tested for effects on learning parallel to those of acute stress. When administered 30 min prior to training, a corticosterone dose (40 mg/kg) that enhanced memory on a spontaneous alternation task did not significantly enhance or impair learning in either task. Two doses of epinephrine that modulate memory in other settings were used to test the effects of epinephrine on learning. Pre-training injections of 0.03 mg/kg epinephrine impaired place learning, while 0.1 mg/kg epinephrine impaired response learning. The epinephrine results mimicked those seen with acute stress on the place task, but were opposite those seen after acute stress on the response task. Thus, corticosterone does not appear to be a major factor mediating the effects of acute stress on place and response learning and epinephrine is, at most, a partial contributor to these effects.

Introduction

Acute and chronic stress treatments can have substantial influences on learning and memory in both humans and rodents [52], [53], [54], [76], [79], [80], [83]. However, the direction of effects differs across studies, with some reports describing stress-induced enhancements [8], [21], [49], [81], [84], impairments [8], [25], [26], [49], [78], or no effects [90] on learning, memory, and retrieval. Among the variables contributing to different effects of stress on learning and memory are age and sex [11], [12], [13], [20], [45], [82], [83], [93]. Task differences also contribute importantly to the nature of stress effects on learning and memory [8], [64], [76]. For example, stress prior to training resulted in effects of opposite direction on spatial and non-spatial variants of the swim task [37]. Of note, these results were obtained on tasks that are themselves highly stressful to rats, as evident from the magnitude of systemic release of epinephrine and corticosterone initiated by swimming procedures [7], [37], [48], [75]. One goal of the present experiment was to determine if stress similarly or differently affected place and response learning in appetitive tasks. The present experiments used two versions of a T-shaped maze to address this question. Lesions or inactivation of the hippocampus and striatum impair place and response learning, respectively, in tasks like these and sometimes enhance learning in the opposite task [15], [31], [35], [50], [62], [63], [78]. Such findings suggest that the respective neural systems may compete with each other for control over learning strategy [31], [40], [67], [91].

Another variable that may influence the effects of stress on learning and memory is whether the stress is administered in a single session, i.e., acute stress, or across many days, i.e., chronic stress. Although many studies have investigated the effects of acute stress on learning and memory (e.g., [20], [21], [25], [26], [36], [37], [38], [77], [82]) and others have examined the effects of chronic stress on learning and memory (e.g., [11], [12], [13], [39], [44], [52], [53], [54]), comparisons of effects of acute vs. chronic stress on learning and memory are generally lacking. One study compared different lengths of chronic stress administration, finding that a chronic stress regimen of 6 h/day for 21 days, but not shorter regimens, caused spatial memory deficits [58]. In that experiment, the stress sessions ended 24 h prior to training. In contrast, most assessments of the effects of acute stress on learning and memory involve administration of stress near the time of training, i.e., either posttraining manipulations of stress or stress hormones [26], [33], [73] or pre-training manipulations, ending within 1 h or less before training [37], [38], [66]. However, several studies have revealed proactive effects of stress that last at least 24 h after a stress session [21], [81], [95]. The present experiment compared the effects of repeated or single stress sessions, with repeated stress ending 24 h prior to training and single stress ending either 30 min or 24 h before training.

The overall hypothesis was that prior repeated and single stress would impair learning in a place task, but enhance learning in a response task. This hypothesis was supported only for a single 60-min stress treatment ending 30 min prior to training. A second hypothesis was that the stress-related hormones, corticosterone and epinephrine, would have effects on learning like those of stress. However, corticosterone had no effect on learning and epinephrine impaired learning in both place and response tasks, suggesting that these hormones are not the primary mediators of stress effects on place and response learning.