SELECTIVE EFFECTS OF PERIPHERAL LIPOPOLYSACCHARIDE ADMINISTRATION ON CONTEXTUAL AND AUDITORY-CUE FEAR CONDITIONING

The reported experiments explore the effects of peripheral LPS adminis tration on learning and memory processes. As measured by the condition ed freezing response, intraperitoneal LPS administration given after c onditioning impaired contextual but not auditory-cue fear conditioning in both juvenile (hooded Long Evans) and adult rats (albino Sprague D awley) of two different strains. This impairment in contextual fear co nditioning was not dependent on the presence of the tone. Preexposure to the context eliminated the effect of LPS on contextual fear conditi oning, and in addition, LPS given after context preexposure negated th e beneficial effects of preexposure on contextual fear. These results suggest that LPS disrupts posttrial memory consolidation processes. In support of the hypothesis that LPS-induced proinflammatory cytokine r elease is involved in producing the impairment in contextual fear caus ed by LPS, peripheral interleukin-l receptor antagonist (IL-1 ra) admi nistered subcutaneously at a dose of 100 mg/kg prevented the impairmen t in contextual fear caused by LPS. These experiments provide evidence for a role of immune activation and cytokine activity in learning and memory processes. (C) 1998 Academic Press.