Corticotropin-releasing factor modulation of serotonin release: Neurochemical and behavioral studies in the rat
Abstract
The serotonergic dorsal raphe nucleus (DRN) is innervated by corticotropin-releasing factor (CRF) fibers and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. Studies described in this thesis used in vivo microdialysis in awake behaving rats in order to investigate the potential regulation of extracellular serotonin (5-HT) levels by CRF. The first set of studies characterized and compared the effects of CRF on extracellular 5-HT levels in two terminal regions of the DRN, the lateral septum and striatum. Ventricular administration of CRF produced dose-dependent biphasic effects on extracellular 5-HT levels. A nonselective CRF receptor antagonist blocked these effects. Local infusions of CRF into the DRN, at doses lower than used for ventricular injections, significantly reduced extracellular levels of 5-HT in both the lateral septum and striatum. Furthermore, infusions of a nonselective CRF receptor antagonist into the DRN were sufficient to block the effects of ventricular CRF on extracellular 5-HT in both terminal regions. Thus, the effects of CRF on 5-HT release were determined to be due to interactions at the level of 5-HT cell bodies within the DRN. In the second set of studies the functional significance of CRF regulation of 5-HT release was examined using forced swimming as an environmental and psychological stressor. It was determined that endogenous CRF modulates 5-HT release during forced swimming and that CRF is responsible for the desensitized response of the 5-HT system following forced swimming. Taken together, the experiments in this thesis have important implications for understanding the interactions between two systems, CRF and 5-HT, that exert prominent roles in stress and stress-related neuropsychiatric disorders. ^
Subject Area
Biology, Neuroscience
Recommended Citation
Michelle Lynn Price,
"Corticotropin-releasing factor modulation of serotonin release: Neurochemical and behavioral studies in the rat"
(January 1, 2000).
Dissertations available from ProQuest.
Paper AAI9989641.
http://repository.upenn.edu/dissertations/AAI9989641
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