Regulation of the norepinephrine transporter by chronic administration of antidepressants.
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.
Benmansour
Saloua
S
Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Altamirano
Alfonso V
AV
Jones
David J
DJ
Sanchez
Teresa A
TA
Gould
Georgianna G
GG
Pardon
Marie Christine
MC
Morilak
David A
DA
Frazer
Alan
A
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
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