title: Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy.
abstract: 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.
authors: Division of Clinical Neurosciences, University of Southampton; LD70, South Academic Block, Southampton General Hospital, Southampton SO166YD, UK.
authors: Lisa
authors: L
authors: Barkas
authors: Edward
authors: E
authors: Redhead
authors: Matthew
authors: M
authors: Taylor
authors: Anan
authors: A
authors: Shtaya
authors: Derek A
authors: DA
authors: Hamilton
authors: William P
authors: WP
authors: Gray
mesh_terms: D000328:Adult; D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D008875:Middle Aged; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
chemical_list: D005473:Fluoxetine