[Effects of paroxetine on protein kinase PKA, PKC and CaMKII activity in different brain regions in a rat depression model].
OBJECTIVE
To evaluate the effects of paroxetine on protein kinase PKA, PKC and CaMKII activities in different brain regions in a rat model of depression.


METHODS
Thirty-six adult male SD rats were randomized into 6 groups, including one control group (I) and 5 groups of depression model established by forcing the rats to swim for 4 weeks. The 5 depression groups received no treatment (II) or were treated with paroxetine at a single dose (III), for a week (IV), 2 weeks (V) or 4 weeks (VI). The radioactivity of PKA, PKC and CaMKII in the hippocampus and prefrontal cortex was quantitatively measured using a liquid scintillation counter.


RESULTS
In the rat hippocampus, PKA and CaMKII activities were significantly lower in groups II, III, IV, and V than in groups I and VI (P<0.01 or P<0.05), but comparable between groups VI and I (P>0.05). PKC activity was significantly lower in group II than in group I (P<0.01), but showed no significant difference between the paroxetine-treated groups and group I (P>0.05). In the prefrontal cortex, the activity of PKA in groups I, II, III, and IV was similar (P>0.05), but all significantly lower than that in groups V and VI (P<0.01). PKC activity was significantly higher in groups II and III than that in group I and other paroxetine-treated groups (P<0.01), and similar between groups IV and I (P>0.05); groups V and VI had significantly lower PKC activity than group I (P<0.01). Group I had the highest CaMKII activity among the groups (P<0.01).


CONCLUSIONS
Chronic administration of paroxetine can reverse chronic stress-induced inhibition of PKA, PKC and CaMKII activity in rat hippocampus, while the effects of paroxetine on the protein kinases can be more complex in prefrontal cortex.
Zheng
Hui
H
Guangdong Food and Drug Vocational College, Guangzhou 510520, China. hzheng1203@sina.com
Ma
Guang-yu
GY
Fu
Xiao-chun
XC
DU
Hong-guang
HG
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003863:Depression / Q000201:enzymology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats
D017374:Paroxetine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2