Effect Of Neurosteroid Dehydroepiandrosterone Sulfate (DHEAS)

Defense Date


Graduation Date

Spring 1-1-2007


Campus Only

Submission Type


Degree Name





School of Pharmacy

Committee Chair

David A. Johnson

Committee Member

Paula Witt-Enderby

Committee Member

Robert B. Gibbs


192 IgG-Saporin, Acetylcholine, Dementia, DHEAS, GABA, Passive Avoidance, Rats


Memory is stored in the brain as unique patterns called engrams. Neurotransmitter mediated excitation of these engrams is responsible for recollection. Memory loss is a result of neuronal death due to age or disease. Acetylcholine is an excitatory neurotransmitter in the brain and loss of cholinergic neurotransmission has been associated with memory loss in diseases like AD and dementia. The hippocampus is the site of storage of short-term memory and also plays an essential role in memory consolidation in the brain. The current study investigated the effects of cholinergic hypofunction, induced by lesioning the septohippocampal tract with cholinergic selective immunotoxin 192-IgG Saporin (SAP), on memory acquisition and retention ability of rats in the passive avoidance paradigm. Results indicated that with SAP lesioning there was a significant impaired passive avoidance retention in the animals while memory acquisition remained unaffected. There was no effect of SAP on the locomotor or motivational behavior of the animals. The effects of neurosteroid DHEAS on this SAP induced memory impairment were also studied. DHEAS enhances cholinergic functioning in the brain by negatively modulating GABA and agonizing sigma-1 receptors. Results demonstrated that at DHEAS dose-dependently reversed this impairment in passive avoidance retention in SAP-treated animals, with maximum effect at 10mg/kg dose. No effect on the ability to acquire new memory was observed. DHEAS however did not demonstrate any memory-enhancing effects in animals with cholinergically intact hippocampus indicating that pneumonic effects of DHEAS may only be present during a state of cholinergic hypofunction. These findings suggest that DHEAS may be of therapeutic benefit in cases of memory loss due to cholinergic hypofunctioning, as observed in dementia and AD.





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