Antidepressant effects on kinase gene expression patterns in rat brain.
Multiple kinase pathways determine serotonin transporter (SERT) regulation. We hypothesized a decrease in kinase expression with chronic selective serotonin reuptake inhibitor (SSRI) administration necessary to regulate extracellular serotonin. We studied whole brain kinase mRNA expression on Affymetrix gene chips in rats treated with placebo 3 and 21 days, fluoxetine 3 and 21 days, and citalopram 21 days. Protein kinase C (PKC)-delta, PKC-gamma, stress-activated protein kinase, cAMP-dependent protein kinase beta isoform, Janus protein kinase, and phosphofructokinase M were all down regulated chronically with citalopram and fluoxetine, but not with acute fluoxetine. The results are consistent with homeostasis of SERT function through a decrease in PK expression.
Rausch
J L
JL
Veterans Administration, Medical College of Georgia, Augusta, GA 30912, USA. jeffreyr@mail.mcg.edu
Gillespie
C F
CF
Fei
Y
Y
Hobby
H M
HM
Stoming
T
T
Ganapathy
V
V
Leibach
F H
FH
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010770:Phosphotransferases / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013997:Time Factors
D018687:Antidepressive Agents, Second-Generation; D012333:RNA, Messenger; D005473:Fluoxetine; D015283:Citalopram; D010770:Phosphotransferases