The effects of fluoxetine and environmental enrichment on recovery of function following focal dentate gyrus lesions

UNCW Author/Contributor (non-UNCW co-authors, if there are any, appear on document)
Michael Salling (Creator)
The University of North Carolina Wilmington (UNCW )
Web Site:
Julian Keith

Abstract: New neurons are formed in the dentate gyrus of the mammalian hippocampus throughout adulthood. Rates of adult neurogenesis can be manipulated by pharmacological and environmental factors. Specifically, two factors that lead to increased neurogenesis are the antidepressant fluoxetine which increases the proliferation of neural progenitor cells and environmental enrichment which increases neuronal survival. Although the putative function of adult neurogenesis is unknown, there is accumulating evidence that it plays a role in hippocampal-dependent learning and memory and as a self-repair response following brain insult. The aim of the present study was investigate whether increasing neurogenesis in rats could promote a recovery of spatial function following dentate gyrus damage. Intradentate infusions of colchcine selectively ablated the majority of dorsal dentate gyrus granule cells. Rats where then tested on the Morris water maze and matched to treatment groups. In the treatment paradigm aimed at increasing rates of neurogenesis, rats were given daily saline or fluoxetine injections and either lived in standard housing or a novel enriched environment for 5 weeks with BrdU injections occurring in the middle. Ki67-staining revealed a decrease in cell proliferation associated with the enriched environment. Doublecortin-staining revealed that fluoxetine increased cell survival in the standard housing. BrdU/NeuN-colabeling qualitatively revealed that neurogenesis did occur in the damaged dentate gyrus, but at a low rate. Overall, dentate gyrus lesions significantly decreased the proliferation and survival of new neurons following treatment. We concluded that the colchicine dose used profoundly disrupted the neurogenic niche and that the enriched environment was inhibiting proliferation because it was more stressful than the standard housing. In the post-treatment behavioral testing, lesion rats had significant spatial memory deficits but did improve and enriched rats improved more than standard housed rats. On the probe test, lesion rats outperformed sham rats and lesion rats in the enriched environment outperformed all other rats on target search but not target crossings which may be interpreted as an increased resistance to extinction.

Additional Information

A Thesis Submitted to the University of North Carolina Wilmington in Partial Fulfillment of the Requirements for the Degree of Master of Arts
Language: English
Date: 2009
Dentate gyrus--Diseases, Dentate gyrus--Physiology, Developmental neurobiology--Effect of drugs on, Fluoxetine--Research, Nervous system--Regeneration--Effect of drugs on, Presynaptic receptors--Research, Rats--Research
Rats -- Research
Presynaptic receptors -- Research
Dentate gyrus -- Physiology
Fluoxetine -- Research
Dentate gyrus -- Diseases
Developmental neurobiology -- Effect of drugs on
Nervous system -- Regeneration -- Effect of drugs on

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