MEAL PATTERNS IN RESPONSE TO THE INTRACEREBROVENTRICULAR ADMINISTRATION OF INTERLEUKIN-1-BETA IN RATS

Interleukin-1 beta (IL-1 beta) depresses feeding in rats when administered peripherally (in the microgram range) or centrally (in the nanogram range). In the present study, the effects of the intracerebroventricular (ICV, into the third ventricle) microinfusion of recombinant human IL-1 beta (rhlL-1 beta) on the microstructure of feeding in rats maintained ad lib were investigated with a computerized behavioral monitoring system. ICV microinfusion of rhlL-1 beta (0.5 to 4.0 ng/rat) decreased the short- (2 h) and long-term (nighttime) intake of pellets by reducing meal size and meal duration. Eating rate decreased, indicating a greater effect on meal size than on meal duration. Only the highest dose (4.0 ng/rat) decreased nighttime meal frequency and prolonged nighttime postprandial intermeal intervals. Water intake and locomotor activity also decreased. Water intake-to-food intake ratios in the 2.0 and 4.0 ng/rat rhIL-1 beta-treated groups increased, and this indicated a greater effect of rhIL-1 beta on food intake than on water intake. During the following daytime, meal parameters increased, suggesting compensation for the previous nighttime changes. However, these daytime compensatory responses were limited, and the total daily meal parameters were still decreased. The concomitant ICV microinfusion of rhIL-1 beta (1.0 ng) and recombinant human interleukin-l receptor antagonist (rhIL-1ra, 500 ng) completely blocked the changes in the microstructure of behavior induced by rhIL-1 beta. This evidence suggests specificity of IL-1 beta inducing behavioral changes by direct action in the central nervous system.