Fluoxetine in adulthood normalizes GABA release and rescues hippocampal synaptic plasticity and spatial memory in a mouse model of Down Syndrome

• Published in: Neurobiology of disease Vol. 63; pp. 12 - 19
• Main Authors: Begenisic, Tatjana, Baroncelli, Laura, Sansevero, Gabriele, Milanese, Marco, Bonifacino, Tiziana, Bonanno, Giambattista, Cioni, Giovanni, Maffei, Lamberto, Sale, Alessandro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2014; Elsevier
• Subjects: Analysis of Variance; Animals; Antidepressive Agents, Second-Generation - pharmacology; Antidepressive Agents, Second-Generation - therapeutic use; Biophysics; Disease Models, Animal; Down syndrome; Down Syndrome - complications; Down Syndrome - genetics; Down Syndrome - pathology; Electric Stimulation; Fluoxetine; Fluoxetine - pharmacology; Fluoxetine - therapeutic use; GABA; gamma-Aminobutyric Acid - metabolism; Hippocampus - drug effects; Hippocampus - pathology; In Vitro Techniques; Intellectual disability; Maze Learning - drug effects; Memory Disorders - drug therapy; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurology; Neuronal Plasticity - drug effects; Recognition (Psychology) - drug effects; Space Perception - drug effects; Synaptosomes - drug effects; Synaptosomes - metabolism; Ts65Dn mice; GABA; Intellectual disability; Down syndrome; Fluoxetine; Ts65Dn mice
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2013.11.010

Abstract Down syndrome (DS) is the most common genetic disorder associated with mental retardation. It has been repeatedly shown that Ts65Dn mice, the major animal model for DS, have severe cognitive and synaptic plasticity dysfunctions caused by excessive inhibition in their temporal lobe structures. Here we employed a multidisciplinary approach spanning from the behavioral to the electrophysiological and molecular level to investigate the effects elicited by fluoxetine on cognitive abilities, hippocampal synaptic plasticity and GABA release in adult Ts65Dn mice. We report that a chronic treatment with fluoxetine administered in the drinking water normalizes GABA release and promotes recovery of spatial memory abilities, spatial working memory for alternation, and hippocampal synaptic plasticity in adult Ts65Dn mice. Our findings might encourage new experimental attempts aimed at investigating the potential of fluoxetine for application in the treatment of major functional deficits in adult people with DS.