The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats.
BACKGROUND
Increased interleukin-1beta (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.


CONCLUSIONS
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.
Song
C
C
Department of Biomedical Science, AVC, University of Prince Edward Island, Charlottetown, Canada.
Horrobin
D F
DF
Leonard
B E
BE
D000818:Animals; D001143:Arousal / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000097:blood / Q000139:chemically induced; D015232:Dinoprostone / Q000097:blood*; D004298:Dopamine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005239:Fear / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000633:toxicity*; D016753:Interleukin-10 / Q000097:blood*; D008032:Limbic System / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000097:blood*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood
D007375:Interleukin-1; D018377:Neurotransmitter Agents; D016753:Interleukin-10; D012701:Serotonin; D015232:Dinoprostone; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine