Research Institute Neurosciences Free University, Department of Pharmacology, 1081 BT Amsterdam, the Netherlands
Infections and endotoxin (LPS) can affect hypothalamic CRH neurons
and activate the HPA system. This can be prevented by IL-1 receptor
antagonist and mimicked by IL-1. Chronic activation of the HPA
system by repeated or chronic administration of IL-1 (1 week)
to rats is associated with plastic changes in hypothalamic CRH
neurons. Single administration IL-1ß (5 µg/kg
i.p.) to male Wistar or Lewis rats induced a similar form of
neuroplasticity 1-3 weeks later. This is characterized by a
selective increase in coproduction, costorage, and cosecretion
of AVP in hypothalamic CRH neurons. Exposure of IL-1-primed
rats 1-2 weeks later to foot shocks or IL-1 resulted in exaggerated
ACTH and CORT responses as compared to vehicle-primed controls.
Thus, rats are hyperresponsive to stressors weeks after IL-1
exposure. In IL-1-primed animals, CRH binding and CRH- and V1b
receptor mRNA levels in the pituitary glands are not altered
by IL-1 exposure 2 weeks earlier. We conclude that IL-1-induced,
long-lasting hyperresponsiveness to stressors is primarily caused
by functional alterations in the brain that may be directly
related to observed plasticity of hypothalamic CRH neurons.
