Chronic fluoxetine differentially modulates the hippocampal microtubular and serotonergic system in grouped and isolation reared rats.
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.
Bianchi
Massimiliano
M
Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK. massimiliano.bianchi@inserm.fr
Fone
Kevin C F
KC
Shah
Ajit J
AJ
Atkins
Alan R
AR
Dawson
Lee A
LA
Heidbreder
Christian A
CA
Hagan
Jim J
JJ
Marsden
Charles A
CA
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*
D015306:Biogenic Monoamines; D005473:Fluoxetine; D020033:Protein Isoforms; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014404:Tubulin