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An in vivo investigation of the role of the 5-HT(1A) receptor in brain development
A growing body of work suggests that the 5-HT1A receptor plays a critical role in both serotonergic development and in the development of target regions to which 5-HT fibers project. Serotonin has been shown to autoregulate its own development and this process appears to involve the stimulation of 5-HT1A receptors. However, much of the work to date has been done in vitro and only a few studies have investigated the effects of altered 5-HT1A receptor function during development in vivo. The goals of the work presented here were to (1) create and validate an in vivo model of 5-HT1A receptor blockade during development using the selective 5-HT 1A antagonist WAY 100635, and (2) to investigate whether developmental exposure to WAY 100635 produces lasting deficits in the maturation of the serotonergic system and of target regions to which 5-HT fibers project. Prenatal blockade of the 5-HT1A receptor produced a transient decrease in 5-HT1A receptor density at GD 20, but no long lasting changes in 5-HT1A or SERT density. Furthermore, continued treatment with WAY 100635 until PD 14 also failed to produce any changes in 5-HT1A receptor density. Thus, prenatal exposure may cause a transient downregulation of the 5-HT1A receptor, but does not appear to result in lasting changes in the maturation of the serotonergic system and 5-HT target areas detected by the methods described here.
McReynolds, Alison Michelle, "An in vivo investigation of the role of the 5-HT(1A) receptor in brain development" (2002). Doctoral Dissertations Available from Proquest. AAI3056260.