Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism
by
Linthorst AC, Penalva RG, Flachskamm C, Holsboer F, Reul JM.
Max Planck Institute of Psychiatry,
Sections of Neurochemistry and Neuropsychopharmacology,
Kraepelinstrasse 2, D-80804 Munich, Germany.
Eur J Neurosci 2002 Dec;16(12):2441-52


ABSTRACT

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 with D-Phe-CRH12-41. Secondly, the effects of intracerebroventricular administration of CRH and urocortin (0.03-1.0 micro g) 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.
CRH
LHPA
Serotonin
21st century
Ketoconazole
Cortisol blues
Sigma ligands
Drugs and reward
CRH-R antagonists
Stress and aggression
Anxiety and depression
Sedatives and anxiolytics
Glucocorticoids and mood
Stress, depression and the rat
Stress, depression and anxiety
Antidepressants and cell growth
Stress and CRH, corticosteroids and monoamines
Depression, antidepressants and the hippocampus
Stress, dynorphin, dysphoria and the kappa opioid system


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