title: Adolescence fluoxetine increases serotonergic activity in the raphe-hippocampus axis and improves depression-like behaviors in female rats that experienced neonatal maternal separation.
abstract: This study was conducted to examine if fluoxetine, a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral effects of neonatal maternal separation in female rats. Sprague-Dawley pups were separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from PND 35 until the end of the whole experimental period. Rats were either subjected to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses during PND 43-45. Daily food intake and weight gain of both NH and MS pups were suppressed by fluoxetine, with greater effects in MS pups. MS experience increased immobility and decrease swimming in forced swim test. Swimming was increased, although immobility was not significantly decreased, in MS females by adolescence fluoxetine. However, adolescence fluoxetine increased immobility during forced swim test and decreased time spent in open arms during elevated plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females, and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest that decreased 5-HTergic activity in the raphe nucleus is implicated in the pathophysiology of depression-like behaviors, and increased 5-HTergic activities in the raphe-hippocampus axis may be a part of anti-depressant efficacy of fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may contribute to the increased anorectic efficacy of fluoxetine in MS females. Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may be related with fluoxetine-induced depression- and/or anxiety-like behaviors in NH females.
authors.affiliation: Dental Research Institute, Department of Oral and Maxillofacial Surgery, Seoul National University, School of Dentistry, Seoul 110-768, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Yoo
authors.forename: Bom-Taeck
authors.initials: BT
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Vitaly
authors.initials: V
authors.lastname: Ryu
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Kang
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jahng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis; D003863:Depression / Q000188:drug therapy; D004435:Eating / Q000187:drug effects; D001068:Feeding and Eating Disorders / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008426:Maternal Deprivation; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D003345:Corticosterone; D003346:Corticotropin-Releasing Hormone; D005473:Fluoxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors