The locus coeruleus (LC) is a group of norepinephrine (NE)-containing neurons that shows marked NE depletion when rats are exposed to uncontrollable shock. The depletion of NE in the LC region results in an increase in burst-firing of LC neurons. Evidence indicates that an increase in burst-firing of LC neurons results in a decrease in motor activity. Intraperitoneal (ip) administration of lipopolysaccharide (LPS), cell wall of gram-negative bacteria, also causes an increase in burst-firing of LC neurons, apparently via the induction of interleukin-1 (IL-1) in the brain. Ip LPS also results in a decrease in spontaneous motor activity in rats, a behavior that expressed in “sickness behavior.” However, a causal relationship between an increase in burst-firing of LC neurons and a decrease in spontaneous motor activity after ip LPS has not yet been established. Therefore, this manuscript examines the effect of IL-1 acting within the LC region on producing an aspect of sickness behavior - a decrease in spontaneous motor activity — that is seen after ip LPS. We hypothesize that the decrease in spontaneous motor activity that occurs after an injection of ip LPS is mediated by the induction of IL- 1 in the LC region.

Several experiments conducted measured spontaneous motor activity as affected by 1) ip LPS, 2) LPS infused into the LC region or 3) IL-1 infused into the LC or LC surrounding regions. A final experiment tested whether interleukin-1 receptor antagonist (IL-lra) infused into the LC region would block the decrease in spontaneous motor activity in response to an injection of ip LPS.

The results showed that a range of ip LPS doses (5-20 pg/kg), a range of LPS doses (0.1-4.0 ng/rat) or a range of IL-lp doses (0.1-40 ng/rat) infused into the LC region all decreased spontaneous motor activity in a dose-dependent manner. Unexpectedly, an infusion of IL-ip (0.4 ng/rat) into LC surrounding regions did not significantly decrease spontaneous motor activity differently from an infusion of IL-ip (0.4 ng/rat) into the LC region.

Finally, central IL-lra (40 pg/rat) was unable to block or affect the decrease in spontaneous motor activity seen after an injection of ip LPS (10 pg/kg). Collectively, the findings do not support the hypothesis that the decrease in spontaneous motor activity that occurs after an injection of ip LPS is mediated by the induction of IL-1 in the LC region. Although LPS infused into the LC region or IL-ip infused into the LC region decreased spontaneous motor activity, IL-lra was unable to block the decrease in spontaneous motor activity seen after an injection of ip LPS.