Desipramine treatment decreases H-3-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells

The antidepressant desipramine has been shown to decrease synaptic membrane concentrations of the norepinephrine re-uptake transporter (NET) in vivo a nd in vitro, on both an acute and a chronic basis. The possible contributio n of decreased NET synthesis to the chronic downregulation of the NETs has not been definitively established. In this study, we treated SK-N-SHSY5Y ce lls with 100 nM desipramine for 24 or 72 h, and measured H-3-nisoxetine bin ding (as an estimate of NETs) and NET mRNA by quantitative reverse transcri ption polymerase chain reaction. Similar to what has been reported previous ly, membrane 3H-nisoxetine binding was significantly decreased at both 24 a nd 72 h (approximately 50% at both time points). However, a significant dec rease (64 +/- 8% of paired control) of NET mRNA was observed only at the 72 -h time point. We conclude that decreased NET synthesis may contribute to t he chronic, but not acute, effect of desipramine to downregulate the NET. ( C) 1999 Elsevier Science Inc.