RT Journal Article SR Electronic T1 Selective and Divergent Regulation of Cortical 5-HT2AReceptors in Rabbit JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1066 OP 1072 VO 299 IS 3 A1 Vincent J. Aloyo A1 Kuldip D. Dave A1 Tariq Rahman A1 John A. Harvey YR 2001 UL http://jpet.aspetjournals.org/content/299/3/1066.abstract AB It is well established that repeated administration of both 5-hydroxytryptamine2 (5-HT2) receptor agonists and antagonists decreases the density of 5-HT2A and 5-HT2C 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-HT2 receptor agonists (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) and d-lysergic acid diethylamide (LSD) and the antagonistsd-2-bromolysergic acid diethylamide hydrogen tartrate (BOL) and α-phenyl-2-(2-phenylethyl)-4-piperidinemethanol (MDL 11,939) on rabbit cortical 5-HT2A and 5-HT2Creceptors. Repeated administration of DOI, LSD, or BOL decreased cortical 5-HT2A receptor density but had no effect on the density of cortical 5-HT2C receptors. Repeated administration of the selective 5-HT2A receptor antagonist MDL 11,939 significantly increased 5-HT2A receptor density. This unexpected outcome also occurred without any change in cortical 5-HT2C receptor density. The down-regulation of 5-HT2A receptors produced by chronic administration of BOL was associated with a decrease in DOI-elicited head bobs, whereas 5-HT2A receptor up-regulation produced by MDL 11,939 was associated with an increase in DOI-elicited head bobs compared with controls. These studies demonstrate that 5-HT2A receptor antagonists can both down- and up-regulate the density of cortical 5-HT2A receptors and these changes in receptor density have functional consequences for 5-HT2A receptor-mediated behaviors. Furthermore, because DOI, LSD, and BOL have approximately equal affinities for the 5-HT2A and 5-HT2Creceptors, these results suggest that different mechanisms regulate 5-HT2A and 5-HT2C receptor density, in that chronic occupation of 5-HT2C receptors does not modulate their density in rabbit frontal cortex. The American Society for Pharmacology and Experimental Therapeutics