Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy

Barkas, Lisa, Redhead, Edward, Taylor, Matthew, Shtaya, Anan, Hamilton, Derek A. and Gray, William P. (2012) Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy. Brain, 135, (8), 2358-2374. (doi:10.1093/brain/aws176). (PMID:22843410).


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Learning and memory dysfunction is the most common neuropsychological effect of mesial temporal lobe epilepsy, and because the underlying neurobiology is poorly understood, there are no pharmacological strategies to help restore memory function in these patients. We have demonstrated impairments in the acquisition of an allocentric spatial task, in patients with unilateral hippocampal sclerosis. We also show that patients have accelerated forgetting of the learned spatial task and that this is associated with damage to the non-dominant hippocampal formation. We go on to show a very similar pattern of chronic allocentric learning and accelerated forgetting in a status epilepticus model of mesial temporal lobe epilepsy in rats, which is associated with reduced and abnormal hippocampal neurogenesis. Finally, we show that reversal of the neurogenic deficit using fluoxetine is associated with reversal of the learning deficit but not the accelerated forgetting, pointing to a possible dissociation in the underlying mechanisms, as well as a potential therapeutic strategy for improving hippocampal-dependent learning in patients with mesial temporal lobe epilepsy.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1093/brain/aws176
ISSNs: 0006-8950 (print)
1460-2156 (electronic)
Alternative titles: Fluoxetine and learning/memory in TLE
Keywords: epilepsy, epilepsy memory impairment, neurogenesis, mesial temporal sclerosis, spatial memory
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions : Faculty of Medicine > Primary Care and Population Sciences
Faculty of Social and Human Sciences > Psychology > Cognition
ePrint ID: 339774
Accepted Date and Publication Date:
August 2012Published
Date Deposited: 30 May 2012 13:14
Last Modified: 31 Mar 2016 14:29
URI: http://eprints.soton.ac.uk/id/eprint/339774

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