Award Date

12-2010

Degree Type

Thesis

Degree Name

Master of Arts in Psychology

Department

Psychology

First Committee Member

Jefferson Kinney, Chair

Second Committee Member

Daniel Allen

Third Committee Member

Laurel Pritchard

Graduate Faculty Representative

Frank van Breukelen

Number of Pages

91

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder marked by a progressive loss of cognitive function. One of the neurobiological hallmarks of AD is a progressive loss of cholinergic neurons and a decrease in the amount of acetylcholine in the brain. Pharmacological therapies have targeted the cholinergic system, specifically first-line, palliative treatment using acetylcholinesterase (AChE) inhibitors, such as donepezil. Donepezil has been shown to increase cholinergic tone and ameliorate some of the cognitive deficits in AD patients. Galanin, a neuropeptide that inhibits the evoked release of several neurotransmitters including acetylcholine as well as modulates seveal intracellular cascades, is overexpressed in AD resulting in an as yet unidentified modulation of neurobiological function. Galanin also impairs learning and memory when administered centrally to rodents, suggesting it may contribute to the cognitive impairments observed in AD. While the mechanism by which galanin impairs learning has yet to be determined, studies suggest it is through cholinergic mechanisms. We investigated the ability of donepezil to rescue learning and memory deficits induced by galanin administration, and by extension isolated whether the learning impairments produced by galanin were ameliorated by increasing cholinergic tone. We also investigated the effects of donepezil and galanin in an animal model of AD, i.e. their effects on learning and memory following a slight lesion of cholinergic neurons analogous to the cholinergic loss seen in AD. This study provides vital information about the relationship between galanin-induced deficits and acetylcholine, and helps to clarify the roles of donepezil and galanin in AD.

Keywords

Alzheimer's disease; Cholinergic mechanisms; Cholinergic receptors; Donepezil; Galanin; Water maze

Disciplines

Diseases | Nervous System Diseases | Neurosciences | Pathology

Language

English


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