INVOLVEMENT OF 5-HT2A RECEPTORS IN THE ELEVATION OF RAT SERUM CORTICOSTERONE CONCENTRATIONS BY QUIPAZINE AND MK-212

The possible involvement of 5-HT2A or 5-HT2C receptors in the elevatio n of serum corticosterone in rats by quipazine (2-(1-piperazinyl)quino line maleate) and MK-212 (6-chloro-(1-piperazinyl)pyrazine), direct-ac ting 5-HT receptor agonists, was investigated by the use of two newly available receptor antagonists, SB 200646A (N-(1-methyl-5-indolyl)-N'- (3-pyridyl)urea) and MDL 100,907 1-[2-(4-fluorophenylethyl)]-4-piperid inemethanol). MDL 100,907 blocked the increase in serum corticosterone elicited by quipazine and MK-212 with ED(50) values of 0.0028 and 0.0 027 mg/kg, s.c., respectively. In contrast, SB 200646A only partially antagonized the serum corticosterone concentration increases by quipaz ine and MK-212 even at the highest dose tested, 40 mg/kg, i.p. Because published data show the affinities of MDL 100,907 and SB 200646A for 5-HT2C receptors to be nearly identical, whereas the affinity of MDL 1 00,907 for 5-HT2A receptors is 17 500-fold higher than that of SB 2006 46A, our findings suggest that 5-HT2A receptors rather than 5-HT2C rec eptors mediate the serum corticosterone increases by both quipazine an d MK-212.