Peripheral immune activation, cytokines, and behavior: effects of endotoxin exposure on two-way active avoidance conditioning

Abstract

Peripheral administration of lipopolysaccharide (LPS) or interleukin-1 (IL-1) may lead to alterations of CNS function and behavioral changes designated ¿sickness behavior.¿ Further, some experiments show evidence of LPS- and cytokine-mediated alterations in learning and memory. The current study examined the effects of intraperitoneal LPS injections on behavior in a two-way active avoidance conditioning paradigm. Subjects were able to avoid the mild shock stimulus, escape it, or simply endure it. In a series of experiments, subjects treated with LPS 4 hrs prior to testing on day 1, day 2 or every day showed impaired learning by exhibiting fewer avoidance responses than controls. Furthermore, an LPS-induced increase in non-cued inter-trial interval (ITI) crossings was observed during the last portion of testing, suggesting that a significant percentage of their avoidance responses were not conditioned. LPS injections administered immediately after testing on day 1 or 4 hrs prior to testing on day 4 did not produce decrements in the number of avoidance responses. The results suggest that, when administered at specific time points, LPS is capable of altering two-way active avoidance conditioning. Furthermore, LPS-treated animals' behavior suggests that they failed to form a strong association between conditioned stimulus (CS) and unconditioned stimulus (US). These results support the theory that peripheral immune stimuli may induce deleterious effects on learning, and extend the work to a negatively reinforced operant procedure.