DOI, an agonist of 5-HT2A-2C serotonin receptor, alters the expression of cyclooxygenase-2 in the rat parietal cortex

The hallucinogenic effect of DOI, serotonin 5-HT2A/2C receptor agonist, is known to be associated with the activation of cortical 5-HT2 receptors. However, the effect of DOI on excitability of cortical neurons and their subsequent function is still not quite understood. Previous immunohistochemical studies using Fos proteins expression as a marker of neuronal activity showed the involvement of arachidonic acid cascade, particularly cyclooxygenase metabolic pathway, in DOI-induced Fos proteins expression in the rat parietal cortex. DOI increases arachidonic acid release which is transformed itself via acceleration of cyclooxygenase metabolic pathway to biologically active metabolites, such as prostaglandins and tromboxanes. Since cyclooxygenase-2 (COX-2) expression correlates with neuronal activity, it was of interest to investigate whether DOI is capable of influencing the level of COX-2 protein and mRNA expression in the rat parietal cortex. It was observed that neurons which were positive for 5-HT2A receptors showed constitutive COX-2 immunoreactivity. It was found further, that COX-2 protein level was increased at 1h, and returned to the control level at 3 and 6 h after DOI (5 mg/kg) administration. In contrast, DOI decreased the COX-2 mRNA expression at all tested time points (1h, 3h and 6h after DOI treatment). The obtained results further support the suggestion that COX-2 activation and possibly arachidonic acid metabolites generated by COX-2 may be considered as important mediators of functional responses generated by activation of cortical 5-HT2A/2C receptors.