Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome
| Autor: | Susanne Schnell, Devon Ryan, Katharina Paesler, Markus Heinen, Moritz M. Hettich, Dan Ehninger |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
drug effects [Body Weight] Cell Count Hippocampal formation mortality [Seizures] pharmacology [Serotonin Uptake Inhibitors] adverse effects [Serotonin Uptake Inhibitors] Mice Intellectual disability drug effects [Behavior Animal] chemically induced [Seizures] Image Processing Computer-Assisted pharmacology [Selective Serotonin Reuptake Inhibitors] pharmacology [GABA-A Receptor Antagonists] Mice Inbred C3H Behavior Animal GABAA receptor Immunohistochemistry etiology [Memory Disorders] Neurology Serotonin Uptake Inhibitors Antidepressant psychology [Down Syndrome] adverse effects [Fluoxetine] Female Psychology Selective Serotonin Reuptake Inhibitors medicine.drug Research Article Down syndrome Article Subject Genotype Serotonin reuptake inhibitor psychology [Cognition Disorders] pharmacology [Fluoxetine] drug therapy [Memory Disorders] Motor Activity drug effects [Maze Learning] lcsh:RC321-571 drug therapy [Down Syndrome] Seizures Fluoxetine medicine genetics [Down Syndrome] Animals ddc:610 GABA-A Receptor Antagonists Maze Learning lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Memory Disorders drug effects [Motor Activity] Body Weight drug therapy [Cognition Disorders] medicine.disease adverse effects [Selective Serotonin Reuptake Inhibitors] Mice Inbred C57BL Neurology (clinical) Down Syndrome Cognition Disorders Neurocognitive Neuroscience |
| Zdroj: | Neural Plasticity Neural Plasticity, Vol 2012 (2012) Neural plasticity 2012, 1-10 (2012). doi:10.1155/2012/467251 |
| ISSN: | 1687-5443 2090-5904 |
| DOI: | 10.1155/2012/467251 |
| Popis: | Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAAreceptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAAreceptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome. |
| Databáze: | OpenAIRE |
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