Effects of paroxetine on protein kinase PKA, PKC and CaMKII activity in different brain regions in a rat depression model / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effects of paroxetine on protein kinase PKA, PKC and CaMKII activities in different brain regions in a rat model of depression.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Determination of clonidine in rabbit plasma by HPLC-MS / 药学学报

<p><b>AIM</b>To determine clonidine in rabbit plasma by LC-MS.</p><p><b>METHODS</b>The LC-MS system consisted of Waters Alliance 2790 HPLC and Micromass ZQ-4000 MS. The HPLC was performed by using XTerra C18 (150 mm x 2.1 mm ID, 5 microm). The mobile phase, consisting of acetonitrile/ammonium hydrogen carbonate solution, was maintained to a flow-rate of 0.2 mL x min(-1) and the linear gradient elution was adopted. Mass spectrum was obtained by using electrospray ionization interface and the m/z of SIM was 230.</p><p><b>RESULTS</b>The average recovery was high and the method was reproducible. The calibration curve showed good linearity in the range of 1 - 80 microg x L(-1), the lowest limit of detection was 0.05 microg x L(-1). The Cmax, AUC0-t, and Tmax value of the pharmacokinetics parameter were (27 +/- 9) microg x L(-1), (5,352 +/- 1,121) microg x L(-1), (79 +/- 17) h.</p><p><b>CONCLUSION</b>The results demonstrated that the method had high sensitivity, good selectivity, accuracy and precision. It is used to determine the clonidine concentration in plasma. The transdermal patch can deliver clonidine to the surface of rabbit skin stably for periods of up to 1 week after a single application.</p>