PYROGENS SPECIFICALLY DISRUPT THE ACQUISITION OF A TASK INVOLVING COGNITIVE PROCESSING IN THE RAT

In addition to changes in body temperature and other metabolic and phy siological responses corresponding to immune activation, pyrogens can induce profound behavioral changes referred to collectively as sicknes s behavior. One feature of sickness behavior, sometimes reported in cl inical settings, but rarely exposed to experimental analysis, is depre ssed cognitive functioning. The present series of five experiments sou ght to demonstrate the existence of specific cognitive deficits in rat s, independently of any confounding performance effects of pyrogen inj ections. The behavioral task used, called autoshaping, consisted of pr esenting hungry Wistar rats with a stimulus (introduction of a retract able lever) that predicted food delivery. Control rats quickly learned to press the lever, although this response does not influence the pro bability of food delivery. When pyrogens (250 mu/kg lipopolysaccharide , 4 mu g/rat interleukin-1 beta, or 300 mg/rat yeast) were injected to rats during acquisition of this task, they severely disrupted acquisi tion while the pyrogen was active. The same treatments were, however, without effect on performance when injected later, when performance ha d stabilized. II is argued that these results demonstrate specific, pe rformance-independent effects of pyrogens on the cognitive processes n eeded for the acquisition of this task. The results are discussed in t erms of the relationship between these effects and the cytokines induc ed in the brain by pyrogens, and in terms of the exact nature of the c ognitive process likely to be affected. (C) 1995 Academic Press,Inc.