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Linthorst AC, Flachskamm C, Hopkins SJ, et al. Long-term intracerebroventricular infusion of corticotropin-releasing hormone alters neuroendocrine, neurochemical, autonomic, behavioral, and cytokine responses to a systemic inflammatory challenge. J Neurosci. 1997;17(11):4448-60
Linthorst, A. C., Flachskamm, C., Hopkins, S. J., Hoadley, M. E., Labeur, M. S., Holsboer, F., & Reul, J. M. (1997). Long-term intracerebroventricular infusion of corticotropin-releasing hormone alters neuroendocrine, neurochemical, autonomic, behavioral, and cytokine responses to a systemic inflammatory challenge. The Journal of neuroscience : the official journal of the Society for Neuroscience, 17(11), 4448-60.
Linthorst, A C, et al. "Long-term intracerebroventricular infusion of corticotropin-releasing hormone alters neuroendocrine, neurochemical, autonomic, behavioral, and cytokine responses to a systemic inflammatory challenge." The Journal of neuroscience : the official journal of the Society for Neuroscience vol. 17,11 (1997): 4448-60.
Linthorst AC, Flachskamm C, Hopkins SJ, Hoadley ME, Labeur MS, Holsboer F, Reul JM. Long-term intracerebroventricular infusion of corticotropin-releasing hormone alters neuroendocrine, neurochemical, autonomic, behavioral, and cytokine responses to a systemic inflammatory challenge. J Neurosci. 1997 Jun 01;17(11):4448-60. PMID: 9151762; PMCID: PMC6573557.
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J Neurosci. 1997 Jun 01;17(11):4448-60.

Long-term intracerebroventricular infusion of corticotropin-releasing hormone alters neuroendocrine, neurochemical, autonomic, behavioral, and cytokine responses to a systemic inflammatory challenge.

The Journal of neuroscience : the official journal of the Society for Neuroscience

A C Linthorst, C Flachskamm, S J Hopkins, M E Hoadley, M S Labeur, F Holsboer, J M Reul

Affiliations

  1. Max Planck Institute of Psychiatry, Clinical Institute, Department of Neuroendocrinology, Section Neuroimmunoendocrinology, 80804 Munich, Germany.

PMID: 9151762 PMCID: PMC6573557
Free PMC Article

Abstract

Corticotropin-releasing hormone (CRH) was infused intracerebroventricularly into rats for 7 d via a miniosmotic pump (1 microg . microl-1 . hr-1). Body temperature and locomotor activity were recorded during the treatment using biotelemetry, whereas hippocampal serotonergic neurotransmission and free corticosterone levels were monitored using in vivo microdialysis on day 7 of CRH treatment. During the microdialysis experiment, behavioral activity was scored by assessing the time during which rats were active (locomotion, grooming, eating, drinking). Continuous intracerebroventricular infusion of CRH produced a transient increase in body temperature and locomotion. Moreover, intracerebroventricularly CRH-treated rats showed elevated free corticosterone levels with no apparent diurnal rhythm. Intraperitoneal administration of bacterial endotoxin -lipopolysaccharide (LPS); 100 microg/kg body weight- on day 7 of CRH/vehicle treatment produced a marked fever response in control animals, which was significantly blunted in intracerebroventricularly CRH-treated rats. Although free corticosterone levels reached similar peak concentrations in both intracerebroventricularly vehicle- and CRH-infused groups after LPS, this response was delayed significantly by approximately 1 hr in the intracerebroventricularly CRH-treated animals. Microdialysis experiments showed no changes in basal extracellular levels of serotonin and 5-hydroxyindoleacetic acid in intracerebroventricularly CRH-infused animals. Injection of LPS in intracerebroventricularly CRH-treated rats produced a blunted 5-HT response and a delayed onset of behavioral inhibition and other signs of sickness behavior. Assessment of the endotoxin-induced cytokine responses showed significantly enhanced plasma interleukin-1 (IL-1) and IL-6 bioactivities in the intracerebroventricularly CRH-infused animals 3 hr after injection of LPS, whereas tumor necrosis factor bioactivity responses were not different. Our data demonstrate that chronically elevated brain CRH levels produce marked changes in basal (largely CRH regulated) physiological and behavioral processes accompanied by aberrant responses to an acute challenge. The present study provides evidence that chronic CRH hypersecretion is an important factor in the etiology of stress-related disorders.

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