Inhibition of arachidonic acid cascade attenuates the induction of c-Fos proteins by DOI, 5-HT2A/2C receptor agonist, in the rat cortex.
Previous immunohistochemical studies have shown that c-Fos proteins induced by DOI, a 5-HT2A/2C agonist, are present in the population of cortical neurons, which are devoid of 5-HT2A receptors. A mechanism of the induction of c-Fos proteins expression by DOI is still unclear. However, the involvement of the 5-HT2A and AMPA, but not 5-HT2C receptors in this process has been reported. In the present study, we investigated whether arachidonic acid, a retrograde messenger, is involved in the above mechanism of c-Fos induction. Phospholipase A2 pathway, which leads to the subsequent generation of arachidonic acid and its metabolites, is known to be coupled to 5-HT2A receptor activation. The inhibition of arachidonic acid cascade both at the level of phospholipase A2 (by dexamethasone, 1.5 mg/kg) or at the level of cyclooxygenases that catalyze arachidonic acid biotransformation (by indomethacin, 3 mg/kg), decreased the number of c-Fos immunopositive cells after induction by DOI (8 mg/kg). Our results suggest that arachidonic acid cascade may be involved in the induction of c-Fos proteins by DOI in the rat parietal cortex.
Maćkowiak
Marzena
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków. mackow@if-pan.krakow.pl
Czyrak
Anna
A
Wedzony
Krzysztof
K
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors*; D003907:Dexamethasone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D016760:Proto-Oncogene Proteins c-fos; D017366:Serotonin Receptor Agonists; D016718:Arachidonic Acid; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D007213:Indomethacin