Regulation of serotonin(2A) receptor expression by an antisense oligodeoxynucleotide

Abstract

The regulation of 5-HT(2A) receptor expression by an antisense oligodeoxynucleotide, complementary to the coding region of rat 5-HT(2A) receptor mRNA, was examined in a cortically derived cell line and in rat brain. Treatment of A1A1 variant cells, which express the 5-HT(2A) receptor coupled to the stimulation of phosphatidylinositol (PI) hydrolysis, with antisense oligodeoxynucleotide decreased the maximal stimulation of PI hydrolysis by the partial agonist quipazine and the number of 5-HT(2A) receptor sites as measured by the binding of 2,[125I] iodolysergic acid diethylamide. Treatment of cells with random, sense, or mismatch oligodeoxynucleotide did not alter the stimulation of PI hydrolysis by quipazine or 5-HT(2A) receptor number. Intracerebroventricular infusion of antisense, but not mismatch, oligodeoxynucleotide for 8 days resulted in a significant increase in cortical 5-HT(2A) receptor density and an increase in headshake behavior induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy 4- iodophenyl)-2-aminopropane. The density of cortical 5-HT(2A) receptors was not altered by administration of antisense oligodeoxynucleotide for 1, 2, or 4 days. We hypothesize that in brain this antisense oligodeoxy-nucleotide relieved some form of translational suppression, resulting in an increase in 5-HT(2A) receptor expression.