title: Effects of desipramine treatment on stress-induced up-regulation of norepinephrine transporter expression in rat brains.
abstract: BACKGROUND
  Many studies demonstrate down-regulation of the norepinephrine transporter (NET) by desipramine (DMI) in vitro and in stress-naive rats. Little is known regarding regulation of the NET in stressed animals.
  
  
  OBJECTIVE
  The present study was designed to investigate effects of DMI on the expression of NET and protein kinases in the stress rat.
  
  
  METHODS
  Adult Fischer 344 rats were subjected to chronic social defeat (CSD) for 4 weeks. DMI (10 mg/kg, intraperitoneal (i.p.)) was administered concurrently with CSD or 1 or 2 weeks after cessation of CSD. Sucrose consumption, NET expression, and protein kinases were measured.
  
  
  RESULTS
  CSD significantly increased messenger RNA (mRNA) and protein levels of NET in the locus coeruleus, as well as NET protein levels in the hippocampus, frontal cortex, and amygdala. These effects were nearly abolished when DMI was administered concurrently with CSD. CSD-induced up-regulation of NET expression in the locus coeruleus, hippocampus, and amygdala lasted at least 2 weeks after cessation of CSD, an effect that was significantly attenuated by 1 or 2 weeks of DMI treatment starting from cessation of the CSD. Concurrent administration of DMI with CSD did not markedly interfere with CSD-induced decreases in protein levels of protein kinases A and C in these brain regions, but it did reverse the CSD-induced reduction in phosphorylated cAMP response element-binding (pCREB) protein levels in most brain regions.
  
  
  CONCLUSIONS
  These findings suggest that NET regulation by DMI occurs in both stressed and behaviorally naive rats, and DMI-induced changes in pCREB may be involved.
authors.affiliation: Departments of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37604, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ordway
authors.forename: Meng-Yang
authors.initials: MY
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D011494:Protein Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013315:Stress, Psychological / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D011494:Protein Kinases; D003891:Desipramine