Spatial Learning Responses to Lipopolysaccharide in Adult and Aged Rats

Sickness behaviors, adaptive responses to infections, include lethargy, depression, reduced eating and grooming, and concentration problems resulting from interactions between the immune and neuroendocrine systems. Detecting these responses is especially critical in the elderly, as the infections that cause them can lead to cognitive impairment. While deficits in spatial learning, a hippocampal-dependent form of learning, are part of the sickness response, directional heading errors (DHEs; an indicator of spatial-learning deficits) and their time trajectories need further examination. Therefore, we simultaneously investigated the time trajectory of age-dependent sickness responses and spatial learning over 5 days in adult (5-6 months) and aged (22 months) male Brown-Norway rats injected with 250 g/kg lipopolysaccharide (LPS; experimental group) or 0.9% sodium chloride (control group). LPS administration resulted in pronounced, age-dependent weight loss and decreased food intake that persisted in the aged group. Animals were tested for 5 days (trial) in the Morris water maze. After 7 days of rest, animals were retested for 2 days (retention). Adult and aged LPS-treated animals displayed greater differences in mean DHE than the control groups, indicating that they exhibited more DHE over the trial days. Experimental groups did not show consistent DHE improvement until Day 4 (adult) or 5 (aged). LPS had no effect on probe or retention trials. We conclude that LPS activation of the immune system results in a selective, age-dependent impairment in spatial learning, decreased food intake, and weight loss. All of these results are prolonged in aged animals.