Behavioral changes in rats after acute, chronic and repeated administration of Interleukin-1beta: relevance for affective disorders

Background: Acute, peripheral and central administration of recombinant rat interleukin-1β (IL-1β) has been shown to decrease social exploration and locomotor activity and to induce alterations in brain biogenic amines in rats. The aims of this study were to examine whether acute, repeated and chronic administration of IL-1β to rats may interfere with shuttle box escape learning, a model for anxiety- and depression-like behavior. Methods: Sixty-four adult male viral-free Sprague–Dawley rats (200–300 g weight) housed in groups of four at 25 °C with a 12:12 light:dark cycle were used in the experiments. They were divided into 8 groups, i.e. 4 control and 4 experimental. The latter were divided into an acute group receiving a single intra-peritoneally (I.P.) challenge of IL-1β (tested at the shuttle box 1 and 24 h later); a chronic group with daily I.P. injections of IL-1β for 7 days (tested at the shuttle box 1 h later); and a group with repeated administration, i.e. one I.P. injection on the first day and a second challenge on the seventh day (tested at the shuttle box 1 h later). The control animals followed the same injecting and testing schedule but were treated I.P. with saline. Results: The acute group treated with one IL-1β challenge and tested 1 (P=0.001) and 24 h (P=0.002) later showed significant time elongations in the escape trials. The animals treated chronically with IL-1β for seven consecutive days showed a significant increase in the latency at the escape trials (P=0.0001). Repeated administration of IL-1β on the first day and a second on the seventh day did not significantly alter the time elongation in the escape trial. Discussion: Acute and chronic administration of IL-1β significantly increase the latency of escape to a foot shock, whereas repeated IL-1β administration does not induce a sensitization of these behavioral responses.