Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism.
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 microg) 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.
Linthorst
Astrid C E
AC
Max Planck Institute of Psychiatry, Section of Neurochemistry, Kraepelinstrasse 2, D-80804 Munich, Germany. linthors@mpipsykl.mpg.de
Peñalva
Rosana G
RG
Flachskamm
Cornelia
C
Holsboer
Florian
F
Reul
Johannes M H M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013550:Swimming / Q000523:psychology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D054832:Urocortins
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C113202:phenylalanyl corticotropin-releasing factor (12-41); D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003346:Corticotropin-Releasing Hormone