Lipopolysaccharide induces a spinal learning deficit that is blocked by IL-1 receptor antagonism

Abstract

Previous studies have shown that spinal neurons are capable of supporting a form of instrumental conditioning. Subjects receiving a spinal transection will learn to maintain a flexion response after exposure to shock contingent on leg position. In contrast, subjects receiving shock irrespective of leg position will not show increased flexion duration. Activation of the immune system has deleterious effects on learning in intact animals, but the impact of immune system activation on learning spinal animals is not known. We found that a large dose of i.p. LPS (1.0mg/kg) significantly disrupted the acquisition of the instrumental flexion response. The LPS-induced learning deficit was not prevented by preexposure to contingent shock (i.e. immunization) (Experiment 2). Co-administration of the iNOS inhibitor L-NIL (0.1, 1.0 and 10.0 microg/microL) failed to block the deficit (Experiment 3). Co-administration of an IL-1 receptor antagonist (r-metHuIL-1ra [10.0, 30.0 and 100.0 microg/microL) prevented the LPS-induced learning deficit when given in a dose of 100.0 microg/microL(i.t.) only (Experiment 4). Findings indicate a role for spinal IL-1 in the decreased plasticity following LPS administration.