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Selective stress-induced sensitivity of 5-HT neurons following chronic fluoxetine administration
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2015 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

BACKGROUND: The serotonin (5-HT) system is strongly implicated in depression. Serotonergic projections originating from the brain-stem nuclei dorsal raphe (DR) and median raphe (MR) provide highly organized innervation to the forebrain. It is poorly understood how these neurons dysfunction in depression, and whether the dysfunction displays topographical specificity. Moreover, it remains unclear how chronic treatment with selective serotonin re-uptake inhibitors (SSRI’s) during depression alters 5-HT neuronal function.

AIM: To study potential stress-induced dysfunction of 5-HT neuronal subpopulations in DR and MR in a rodent depression model. Furthermore, to examine how chronic SSRI treatment modifies this dysfunction.

METHODS: A depression model was used wherein rats were subjected to neonatal maternal separation (MS). In adulthood, half of the animals received chronic subcutaneous injections of the SSRI fluoxetine (FLX). After exposure to acute swim stress, serotonergic neuron activity was quantified by immunohistochemistry and behavior was evaluated.

RESULTS: FLX administration significantly attenuated stress-induced 5-HT neuronal activity. This effect showed no subregional specificity. Rats subjected to neonatal MS did not show significant neuronal or behavioral differences in adulthood as compared to control animals. In MS animals, FLX induced effects appeared greater in a subregion of the DR, however these results did not reach statistical significance.

CONCLUSIONS: FLX decreases the raphe neuronal response to acute stress. Moreover, adverse early life experiences may lead to subregion specific stress-induced sensitivity to FLX in the DR. Gaining a better understanding of how specific components in the serotonergic system are affected by depression could lead to the development of more targeted and effective treatments.

Place, publisher, year, edition, pages
Keyword [en]
depression, serotonin, 5-HT, tryptophan hydroxylase, maternal separation, forced swim
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-262665OAI: oai:DiVA.org:uu-262665DiVA: diva2:855931
External cooperation
Harvard Medical School / Boston Children's Hospital
Subject / course
Pharmaceutical Biosciences
Educational program
Master of Science Programme in Pharmacy
Available from: 2016-10-06 Created: 2015-09-17 Last updated: 2016-10-06Bibliographically approved

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