Authors: Linthorst, Astrid C. E.; Peñalva, Rosana G.; Flachskamm, Cornelia; Holsboer, Florian; Reul, Johannes M. H. M.

Source: European Journal of Neuroscience, Volume 16, Number 12, December 2002 , pp. 2441-2452(12)

Publisher: Wiley-Blackwell

Abstract:

Summary

Serotonin is important for adequate coping with stress. Aberrant serotonin function is implicated in the aetiology of major depression and anxiety disorders. Dysregulation of the hypothalamic-pituitary-adrenocortical axis, involving elevated corticotropin-releasing hormone (CRH) activity, also plays a role in these stress-related illnesses. Here we studied the effects of stress on hippocampal serotonin and the role of the CRH system using in vivo microdialysis. First, rats were subjected to a forced swim stress, resulting in a dramatic increase in hippocampal serotonin (1500% of baseline), which was associated with the occurrence of diving behaviour. The diving-associated increase in serotonin depended on activation of CRH receptors, as it was antagonized by intracerebroventricular pretreatment withD-Phe-CRH₁₂₋₄₁. Secondly, the effects of intracerebroventricular administration of CRH and urocortin (0.03-1.0 µg) were studied. Both CRH and urocortin caused a dose-dependent rise in hippocampal serotonin (maximally 350% of baseline) and 5-hydroxyindoleacetic acid levels, suggesting the involvement of CRH receptor type 1. Because the effects of urocortin were prolonged, CRH receptor type 2 could play a role in a later phase of the neurotransmitter response. Experiments using adrenalectomized rats showed that CRH-induced serotonin changes were adrenally independent. These data suggest that the raphe-hippocampal serotonin system is able to mount, CRH receptor-dependent, responses to specific stressful situations that surpass the usually observed maximal increases of about 300% of baseline during stress and enhanced vigilance.

Keywords: corticotropin-releasing hormone receptor antagonis; in vivo microdialysis; serotonin; 5-hydroxyindoleacetic acid; urocortin

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1460-9568.2002.02400.x

Affiliations: 1: Max Planck Institute of Psychiatry, Sections of Neurochemistry and Neuropsychopharmacology, Kraepelinstrasse 2, D-80804 Munich, Germany

Publication date: 2002-12-01

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