Date of Award

2000

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Advisor

H. Elliott Albers

Second Advisor

Jay M. Weiss

Third Advisor

Andrew N. Clancy

Fourth Advisor

John M. de Castro

Fifth Advisor

Kim Huhman

Abstract

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.

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