Effects of paroxetine on protein kinase PKA, PKC and CaMKII activity in different brain regions in a rat depression model.
- Author:
Hui ZHENG
1
;
Guang-yu MA
;
Xiao-chun FU
;
Hong-guang DU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Brain; drug effects; enzymology; Calcium-Calmodulin-Dependent Protein Kinase Type 2; metabolism; Cyclic AMP-Dependent Protein Kinases; metabolism; Depression; enzymology; Disease Models, Animal; Hippocampus; drug effects; enzymology; Male; Paroxetine; pharmacology; Protein Kinase C; metabolism; Random Allocation; Rats
- From: Journal of Southern Medical University 2008;28(7):1223-1225
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo evaluate the effects of paroxetine on protein kinase PKA, PKC and CaMKII activities in different brain regions in a rat model of depression.
METHODSThirty-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.
RESULTSIn 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).
CONCLUSIONChronic 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.