title: Regulation of the norepinephrine transporter by chronic administration of antidepressants.
abstract: BACKGROUND
  Downregulation of serotonin transporter was observed previously after chronic treatment with selective serotonin reuptake inhibitors (SSRIs) but not selective norepinephrine reuptake inhibitors (NRIs). This study investigated if chronic treatment of rats with selective NRIs or SSRIs also affected the norepinephrine transporter (NET).
  
  
  METHODS
  Rats were treated for 3 to 6 weeks by osmotic minipumps with either the selective NRIs, desipramine, or the SSRI paroxetine.
  
  
  RESULTS
  [(3)H]nisoxetine binding sites as well as [(3)H]norepinephrine uptake were decreased in hippocampus and cortex after treatment with desipramine. By contrast, paroxetine-treated rats showed no alteration in either [(3)H]nisoxetine binding or [(3)H]norepinephrine uptake. NET messenger RNA levels in the locus coeruleus were unchanged by desipramine treatment.
  
  
  CONCLUSIONS
  These results demonstrate that the marked decrease in NET density 1) is not a consequence of a decrease in gene expression; 2) was caused only by a selective NRI; and 3) was associated with a parallel decrease in norepinephrine uptake.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: Saloua
authors.initials: S
authors.lastname: Benmansour
authors.forename: Alfonso V
authors.initials: AV
authors.lastname: Altamirano
authors.forename: David J
authors.initials: DJ
authors.lastname: Jones
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Sanchez
authors.forename: Georgianna G
authors.initials: GG
authors.lastname: Gould
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Pardon
authors.forename: David A
authors.initials: DA
authors.lastname: Morilak
authors.forename: Alan
authors.initials: A
authors.lastname: Frazer
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D027981:Symporters / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D003891:Desipramine; D005473:Fluoxetine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; C493226:Slc6a2 protein, rat; C011386:nisoxetine