Effects of low-dose lipopolysaccharide and age on spatial learning in different Morris water maze protocols

Abstract

Objectives: Animals administered lipopolysaccharide exhibit dose-related sickness behaviors (decreased food intake, weight loss, and cognitive changes). While research has demonstrated that spatial learning is impaired following a lipopolysaccharide immune challenge, the results differ depending on the methodology used to evaluate spatial learning. Additionally, few studies have evaluated the effects of low-dose lipopolysaccharide on spatial learning. Therefore, we assessed spatial learning, food intake, and weight changes in adult and aged rats after a low-dose lipopolysaccharide immune challenge in the Morris water maze using two water temperatures.

Methods: Adult (5-6 months) and aged (22 months) male Brown-Norway rats were administered either 50 or 100 μg/kg lipopolysaccharide or saline, and then tested in the Morris water maze for 5 days, rested for 7 days, and later underwent 2 days of retention tests. Probe trials were conducted at the end of initial and retention testing.

Results: Low-dose lipopolysaccharide administration did not result in food intake or weight changes. While the aged experimental group took longest to improve directional heading error in both cold and warm water, heading error was greater in cold water. Behavioral testing revealed an apparent age and water temperature effect on swim time. Retention and probe trial results showed that aged experimental animals had the worst performance in cold water.

Conclusion: We conclude that while low-dose lipopolysaccharide did not result in typical sickness behaviors (decreased food intake or weight), spatial learning and memory were impaired in the aged experimental group. These results have important implications for the care of elderly individuals experiencing mild to moderate infections.

Keywords: Aging; illness behavior; lipopolysaccharide; maze learning; memory; time factors.

Figure 1.

Effect of lipopolysaccharide on mean food intake across the days for aged and adult rats tested in (a) cold water and (b) warm water. Error bars represent ±SE (standard error of the mean). **p < .01 for the aged groups (experimental and control groups combined) in comparison with the adult groups on the pre-injection day in warm water (b). ***p < .001 for all four groups comparing cold and warm water on post-injection day 2. Cold water, n = 2 per group; warm water, n = 4 per aged groups, n = 2 per adult groups.

Figure 2.

Effect of lipopolysaccharide on mean weight loss across the days for aged and adult rats tested in (a) cold water and (b) warm water. Error bars represent ±SE (standard error of the mean). Cold water, n = 2 per group; warm water, n = 4 per aged groups, n = 2 per adult groups.

Figure 3.

Effect of lipopolysaccharide on mean directional heading error in adult and aged rats tested in (a) cold water and (b) warm water. Error bars represent ±SE (standard error of the mean). Cold water, n = 2 per group; warm water, n = 4 per aged groups, n = 2 per adult groups.

Figure 4.

Effect of lipopolysaccharide on mean swim latency in adult and aged rats tested in (a) cold water and (b) warm water. Error bars represent ±SE (standard error of the mean). Trial days 1–5: main effects—*p < .05 for water and **p < .01 for age (control and experimental groups combined) for days 1–5 over both water conditions; *p < .05 for aged experimental and control groups on post-injection day 3 in (b) warm water. Retention days: ***p < .001 for aged groups (control and experimental combined) in comparison with adult groups in (a) cold water. Cold water, n = 2 per group; warm water, n = 4 per aged groups, n = 2 per adult groups.

Figure 5.

Effect of lipopolysaccharide on mean percent of distance traveled in the correct quadrant in each probe trial (1 and 2) in adult and aged rats tested in (a) cold water and (b) warm water. Error bars represent ±SE (standard error of the mean). *p < .05 across the groups and water conditions for the second probe trial in comparison with the first. Cold water, n = 2 per group; warm water, n = 4 per aged groups, n = 2 per adult groups.