In the present study we have characterized the time course of effect of administration of the serotonin 2 (5-HT 2 ) receptor antagonist mianserin, or the 5-HT 2 receptor agonist (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), on 5-HT 2A receptor binding sites and mRNA levels in rat frontal cortex. Radioligand binding and ribonuclease protection assays were performed with separate hemispheres of frontal cortex from each animal to examine concomitant changes in 5-HT 2A receptor sites and mRNA levels. The decrease in cortical 5-HT 2A receptor sites in response to chronic DOI administration was not accompanied by changes in 5-HT 2A receptor mRNA. A single injection of DOI produced a transient decrease in 5-HT 2A receptor mRNA levels detected 1 h post-injection. The density of 5-HT 2A receptor sites, however, was not significantly reduced following a single injection of DOI. The down-regulation of cortical 5-HT 2A receptor sites in response to a single injection of mianserin was accompanied by reductions in 5-HT 2A receptor mRNA levels. Following 4 days of mianserin administration, however, we did not observe a change in 5-HT 2A receptor mRNA levels, although 5-HT 2A receptor density was decreased. Thus, changes in receptor mRNA may initially contribute to the down-regulation of 5-HT 2A receptors in response to acute mianserin administration. Sustained changes in 5-HT 2A receptor mRNA, however, appear not to be involved in maintaining the down-regulation of 5-HT 2A receptor number with chronic mianserin administration. Mechanisms other than the regulation of receptor mRNA levels appear to underlie the down-regulation of 5-HT 2A receptor sites in response to chronic administration of the agonist DOI.
Neuropharmacology – Elsevier
Published: Oct 1, 2000
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