| Abstract No.: | C-C3100 |
| Country: | Canada |
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| Title: | THE INFLUENCE OF THE ACUTE TREATMENT WITH CITALOPRAM ON THE BRAIN ARACHIDONIC ACID TURNOVER IN OBX AND SHAM RATS |
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| Authors/Affiliations: | 1 Ivan Skelin*; 1 Tomislav Kovacevic; 1 Hiroki Sato; 1 Mirko Diksic;
1 Montreal Neurological Institute, McGill University, QC, Canada
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| Content: | Olfactory bulbectomized (OBX) rat is an animal model of depression. The disturbances of different neurotransmitter and neuromodulatory systems (glutamate, serotonin, dopamine) are present in OBX rats. Citalopram is the most selective SSRI (selective serotonin reuptake inhibitor), exhibiting low affinity for the DA (dopamine) or NA (noradrenaline) transporters. By blocking the (5-HT) serotonin reuptake, citalopram increases the extracellular levels of 5-HT. The increased availability of serotonin in the synapses would be expected to increase the brain arachidonic acid (AA) turnover by stimulating the 5-HT2A/2C receptors, which are coupled to the phospholipase A2 (PLA2) second messenger system, which when activated releases the AA. It was of interest to assess whether the acute application of citalopram (10 mg/kg) would cause differential effects on the PLA2 signaling pathways in OBX rats relative to the Sham-operated rats. Male Sprague-Dawley rats (160-180 g) were assigned into OBX and Sham groups (n=6). Olfactory bulbs were cut along the posterior edge of the window (5.2 mm anterior from bregma) and evacuated using the blunted needle attached to the vacuum pump. The Sham surgery was performed in a same way, except that the bulbs were left intact. The animals were allowed for two weeks to recover from the surgery and develop the OBX syndrome. The [14C]-AA autoradiography has been used to quantify the turnover of brain membrane lipids via the PLA2 second messenger pathway. The rats’ femoral vein and artery were catheterized under the general isoflurane anesthesia (1-3%) and the rats were left to recover for 3 hours. Subsequently rats were injected (i.p.) with citalopram (10 mg/kg). Thirty minutes after the drug injection, animals were injected i.v. with the 20 µCi of the [14C]-AA and the blood samples were taken from the artery until the decapitation, twenty minutes after the injection of the tracer. The brains were extracted, rapidly frozen in isopenthane (-25ºC), and stored at -85ºC until cut in the microtome (-20ºC) to 30 µm thick sections, which were contacted with the Fuji 14C imaging plates for 6 weeks along with C-14 standards. Images were quantified using the MCID image analyzer calibrated with standards. The brain regional incorporation coefficients K* [ml/g/min] were calculated as described by Rapoport et al. (2001). The results were analyzed using the STATISTICA software. MANCOVA test has shown that there was no significant region*group interaction (F(37,296)=0.99; p>0.49). However, MANOVA indicated highly significant difference among the regions in these groups (F(37,296)=109.7; p<0.001). The results of the present study show that there is no difference in the effect of acute dose of 10 mg/ kg day of citalopram on the AA-turnover in the brain between the OBX and Sham rats. This suggests that in the OBX rat signalization via receptors coupled to the PLA2 pathway is not differentially affected by the increase in 5-HT relative to the Sham rats. |
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