title: Chronic fluoxetine differentially modulates the hippocampal microtubular and serotonergic system in grouped and isolation reared rats.
abstract: Social isolation from weaning in rats produces behavioural and hippocampal structural changes at adulthood. Here, rats were group or isolation reared for eight-weeks. Following the initial four-week period of rearing, fluoxetine (10 mg/kg i.p.) was administered for 28 days. Changes in recognition memory, hippocampal monoamines, and cytoskeletal microtubules were investigated. Isolation-rearing for four- or eight-weeks produced recognition memory deficits that were not reversed by fluoxetine. Eight-weeks of isolation decreased alpha-tubulin acetylation (Acet-Tub) and the tyrosinated/detyrosinated alpha-tubulin ratio (Tyr/Glu-Tub), suggesting major alterations in microtubule dynamics and neuronal plasticity. In grouped rats, fluoxetine decreased Acet-Tub without changes in Tyr/Glu-Tub. In isolates, fluoxetine did not affect Acet-Tub but increased Tyr/Glu-Tub. Finally, fluoxetine altered serotonin metabolism in grouped, but not in isolated animals. Therefore, isolation-rearing changes the hippocampal responses of the serotonergic and microtubular system to fluoxetine. These findings show that early-life experience induces behavioural changes paralleled by alterations in cytoskeletal and neurochemical functions.
authors: Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK. massimiliano.bianchi@inserm.fr
authors: Massimiliano
authors: M
authors: Bianchi
authors: Kevin C F
authors: KC
authors: Fone
authors: Ajit J
authors: AJ
authors: Shah
authors: Alan R
authors: AR
authors: Atkins
authors: Lee A
authors: LA
authors: Dawson
authors: Christian A
authors: CA
authors: Heidbreder
authors: Jim J
authors: JJ
authors: Hagan
authors: Charles A
authors: CA
authors: Marsden
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D006234:Handling, Psychological; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012934:Social Isolation; D053719:Tandem Mass Spectrometry / Q000379:methods; D014404:Tubulin / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D005473:Fluoxetine; D020033:Protein Isoforms; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014404:Tubulin