Selective and Divergent Regulation of Cortical 5-HT 2A Receptors in Rabbit ABBREVIATIONS: 5-HT 2 , 5-hydroxytryptamine 2

ABSTRACT It is well established that repeated administration of both 5-hydroxytryptamine 2 (5-HT 2 ) receptor agonists and antagonists decreases the density of 5-HT 2A and 5-HT 2C receptors. However, the regulation of these two receptors has not been studied in the same tissue. Therefore, we examined the effects of repeated daily injections of the 5-HT 2 receptor agonists (Ϯ)-2,5-dimethoxy-4-iodoamphetamine (DOI) and D-lysergic acid diethylamide (LSD) and the antagonists d-2-bromolysergic acid diethylamide hydrogen tartrate (BOL) and ␣-phenyl-2-(2-phenylethyl)-4-piperidinemethanol (MDL 11,939) on rabbit cortical 5-HT 2A and 5-HT 2C receptors. Repeated administration of DOI, LSD, or BOL decreased cortical 5-HT 2A receptor density but had no effect on the density of cortical 5-HT 2C receptors. Numerous researchers have demonstrated in vivo that both 5-hydroxytryptamine 2 (5-HT 2 ) agonist and antagonists down-regulate 5-HT 2A and 5-HT 2C receptors (for reviews, see Although, in vivo, 5-HT 2 agonists and antagonists are capable of down-regulating both 5-HT 2A and 5-HT 2C receptors, the previously reported receptor changes have been measured in different brain regions. Regulation of 5-HT 2A receptors has mainly been studied in the cortex, whereas regulation of 5-HT 2C receptors has been investigated in choroid plexus, brain stem, and spinal cord. Thus, these studies have not addressed the question of whether the regulation of these two receptors occurs in a coordinated manner within the same brain region. In the one case of antagonist-induced 5-HT 2A receptor up-regulation, the effect of SR 46349B on the 5-HT 2C receptor was not examined We examined the effects of several 5-HT 2 receptor agonist