REGULATION OF SEROTONIN(2A) RECEPTOR EXPRESSION BY AN ANTISENSE OLIGODEOXYNUCLEOTIDE

The regulation of 5-HT2A receptor expression by an antisense oligodeox ynucleotide, complementary to the coding region of rat 5-HT2A receptor mRNA, was examined in a cortically derived cell line and in rat brain . Treatment of A(1)A(1) variant cells, which express the 5-HT2A recept or 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 -HT2A receptor sites as measured by the binding of 2-[I-125]-iodolyser gic acid diethylamide, Treatment of cells with random, sense, or misma tch oligodeoxynucleotide did not alter the stimulation of PI hydrolysi s by quipazine or 5-HT2A receptor number. Intracerebroventricular infu sion of antisense, but not mismatch, oligodeoxynucleotide for 8 days r esulted in a significant increase in cortical 5-HT2A receptor density and an increase in headshake behavior induced by the 5-HT2 receptor ag onist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. The density of co rtical 5-HT2A receptors was not altered by administration of antisense oligodeoxynucleotide for 1, 2, or 4 days. We hypothesize that in brai n this antisense oligodeoxynucleotide relieved some form of translatio nal suppression, resulting in an increase in 5-HT2A receptor expressio n.