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Pharmacopsychiatry 2006; 39(3): 88-99
DOI: 10.1055/s-2006-941557
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

The Comparison of Changes in Behavior, Neurochemistry, Endocrine, and Immune Functions after Different Routes, Doses and Durations of Administrations of IL-1β in Rats

C. Song1 , D. F. Horrobin2 , B. E. Leonard3
  • 1Department of Biomedical Science, AVC, University of Prince Edward Island, Charlottetown, Canada
  • 2Laxdale Ltd., Stirling, Scotland, UK (deceased)
  • 3Institute for Brain and Behavior Research, Section of Neurosciences, University of Maastricht, Maastricht, The Netherlands
Further Information

Publication History

Received: 13.5.2005 Revised: 31.11.2005

Accepted: 21.12.2005

Publication Date:
23 May 2006 (online)

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Background: Increased interleukin-1β (IL-1) in the brain and periphery has been associated with neurodegenerative and psychiatric disorders. However, results from different IL-1 sources, administrating routes, doses and treatment duration were inconsistent and confused. The neuroendocrine-immune mechanism by which IL-1-induced behavioral changes occur is still unclear. Methods: In the present study, the acute and sub-chronic effects of rat recombinant IL-1, following either intraperitoneal (ip) or intracerebroventricular (icv) injection, were studied on the behavior, corticosterone secretion, peripheral inflammatory responses and brain monoamines. Results: In the open field apparatus, IL-1 (ip) increased locomotor activity but decreased the activity following icv administration. IL-1 had a greater anxiogenic effect in the elevated plus maze after icv than after ip administration. In the Morris water maze spatial memory was only impaired following sub-chronic and icv administration. Both acute and sub-chronic IL-1 increased the serum corticosterone concentration and decreased the release of the anti-inflammatory cytokine IL-10 from whole blood cultures. However, centrally administered IL-1 increased, while peripherally administered decreased, the release of PGE2 from blood cultures. After sub-chronic administration, the noradrenaline concentration was decreased in several limbic regions, while the turnovers of serotonin and dopamine were increased. Discussion: These results suggest that 1) IL-1 effects depended on the dose, route and duration of administration, and 2) IL-1 enhances the responsiveness of rats to stressful environmental stimuli. In addition, the sub-chronic administration of IL-1 induces behavioral, neurotransmitter, hormonal and immune changes that may be causally implicated in the mechanism of some of psychiatric disorders such as depression.

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Cai Song M.D., Ph. D.

Department of Biomedical Science

AVC

University of Prince Edward Island

550 University Ave.

Charlottetown

Canada C1A 4P3

Phone: +1 902 566 7977

Fax: +1 902 569 4289

Email: cai.song@nrc.gc.ca

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