Age increases vulnerability to bacterial endotoxin-induced behavioral decrements

Peripheral lipopolysaccharide (LPS) or proinflammatory cytokines produce alterations in learning, memory, and other behaviors. Additionally, research has demonstrated that factors such as dose, route of administration, species, strain, gender, and age are important modulatory factors in the effects of endotoxin exposure. Previous research from our laboratory and others indicate that LPS-induced behavioral deficits are greater in older subjects. The current study examined avoidance learning in a negatively reinforced operant procedure (i.e., two-way active avoidance conditioning) following single or repeated intraperitoneal LPS injections in 2- and 12-month-old male C57BL/6J mice. LPS-treated subjects show impaired acquisition of the task regardless of the age of the subject, as these animals performed significantly fewer avoidance responses than controls. However, the effects of LPS administration were more pronounced in the 12-month-old animals, particularly for the subjects given repeated LPS injections. These results support the hypothesis that endotoxin exposure is capable of altering performance in this task in a way that may reflect deficits in learning, and provide evidence that increased age may exacerbate these deleterious behavioral effects.