title: Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice.
abstract: Recent evidence underlines the crucial role of neuronal cytoskeleton in the pathophysiology of psychiatric diseases. In this line, the deletion of STOP/MAP6 (Stable Tubule Only Polypeptide), a microtubule-stabilizing protein, triggers various neurotransmission and behavioral defects, suggesting that STOP knockout (KO) mice could be a relevant experimental model for schizoaffective symptoms. To establish the predictive validity of such a mouse line, in which the brain serotonergic tone is dramatically imbalanced, the effects of a chronic fluoxetine treatment on the mood status of STOP KO mice were characterized. Moreover, we determined the impact, on mood, of a chronic treatment by epothilone D, a taxol-like microtubule-stabilizing compound that has previously been shown to improve the synaptic plasticity deficits of STOP KO mice. We demonstrated that chronic fluoxetine was either antidepressive and anxiolytic, or pro-depressive and anxiogenic, depending on the paradigm used to test treated mutant mice. Furthermore, control-treated STOP KO mice exhibited paradoxical behaviors, compared with their clear-cut basal mood status. Paradoxical fluoxetine effects and control-treated STOP KO behaviors could be because of their hyper-reactivity to acute and chronic stress. Interestingly, both epothilone D and fluoxetine chronic treatments improved the short-term memory of STOP KO mice. Such treatments did not affect the serotonin and norepinephrine transporter densities in cerebral areas of mice. Altogether, these data demonstrated that STOP KO mice could represent a useful model to study the relationship between cytoskeleton, mood, and stress, and to test innovative mood treatments, such as microtubule-stabilizing compounds.
authors.affiliation: INSERM UMRS 952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fournet
authors.forename: Gaetan
authors.initials: G
authors.lastname: de Lavilléon
authors.forename: Annie
authors.initials: A
authors.lastname: Schweitzer
authors.forename: Bruno
authors.initials: B
authors.lastname: Giros
authors.forename: Annie
authors.initials: A
authors.lastname: Andrieux
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Martres
mesh_terms: D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003863:Depression / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D005473:Fluoxetine; D008869:Microtubule-Associated Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C491893:Mtap6 protein, mouse; C114026:desoxyepothilone B