Intracerebroventricular administration of interleukin-1 to mice alters investigation of stimuli in a novel environment.

The behavior of mice administered recombinant interleukin-1 (IL-1) was observed in a novel multicompartment chamber. Doses of human IL-1 alpha (4 pg to 40 ng) injected intracerebroventricularly (ICV) 20 min before testing significantly reduced the mean time mice spent in contact with novel stimuli. No other behavior scored (locomotor activity, grooming, scratching) was significantly affected. Similar results were obtained with murine IL-1 alpha (770 pg or 77 ng) and hIL-1 beta (1 pg to 10 ng). This behavioral change resembled that induced following restraint or ICV injection of corticotropin-releasing factor (CRF). The behavioral effect of ICV IL-1 was lost after it was heated for 10 min at 100 degrees C. Neither the CRF antagonist, alpha-helical CRF9-41 (10 or 20 micrograms ICV) nor the prostaglandin synthesis inhibitor indomethacin (50 mg/kg IP) significantly altered the hIL-1 alpha-induced behavioral changes, but naloxone (0.7 mg/kg SC) or sulpiride (5 mg/kg IP) completely prevented them. Our results suggest that intracerebral administration of IL-1 reduces the exploratory behavior of mice. This effect does not apparently involve CRF or prostaglandins, but may involve opioid and dopaminergic systems. This behavioral response to IL-1 administration is consistent with the behavioral effects of IL-1 reported previously, and strengthens the hypothesis that IL-1 secretion may be responsible for behavioral changes associated with immune activation.