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Relationship between recovery of frontocortical 5HT2A receptor density and PI hydrolysis after chronic treatment
Journal article   Peer reviewed

Relationship between recovery of frontocortical 5HT2A receptor density and PI hydrolysis after chronic treatment

Emmanuelle Andree Danielle Schindler, Vincent J Aloyo and John A Harvey
The FASEB journal, v 22(S2), pp 621-621
Apr 2008
DOI: https://doi.org/10.1096/fasebj.22.2_supplement.621

Abstract

Phosphatidylinositol (PI) hydrolysis is the major signaling system of serotonin2A (5HT2A) receptors. This measure typically reflects receptor density, but discordance in the signal‐density relationship has also been reported. Few in vivo studies carefully consider the recovery period after chronic drug administration, and thus we sought to follow 5HT2A receptor density and PI hydrolysis after pharmacologic manipulation. We treated rabbits with 5HT2A/2C agonist DOI (3umol/kg) for 8 days and sacrificed them 1 to 8 days after last injection. Frontocortical tissue was harvested and analyzed for both 5HT2A receptor density, via saturation binding with [3H]ketanserin, and PI hydrolysis, through [3H]inositol phosphate release from tissue slices. One day after DOI treatment, both receptor density and signaling were significantly decreased. During the recovery period, these measures returned to control levels; however, the two do not correspond at every time point. While receptor density returned to control levels by the 5th recovery day, signaling remained decreased until later in the recovery period. On the 8th recovery day, signaling was increased while density remained at control levels. These findings in general support the signal‐density relationship for 5HT2A receptors, but also indicate points of asymmetry between the two measures. These conditions will be explored in further studies.

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