Neonatal organizational effects of the 5-HT₂ and 5-HT_1A subsystems on adult behavior in the rat

Abstract

Males, females, neonatally androgenized females, and neonatally castrated males were treated over the second week of life with 0.25 mg/kg of either the 5-HT₂ agonist 1-(2,5-dimethoxy-3-iodophenyl)-2-aminopropane HCl (DOI), the 5-HT₂ antagonist ritanserin (Rit), the 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), or the 5-HT_1A antagonist WAY100135 (WAY). Exploration, anxiety, sociosexual preferences, and sexual behavior were measured in adulthood. Agents acting on 5-HT_1A receptors do not appear to affect organization of any of the behavioral systems studied. DOI increased exploratory activity but in females only, which suggests that testosterone antagonizes the stimulatory effect of 5-HT₂ activity on exploration. Neonatal ritanserin selectively reduced anxiety in females, and DOI had a similar effect in androgenized females. This indicates that neonatal 5-HT₂ activity is anxiogenic in normal females, anxiolytic in androgenized females, and has no effect on anxiety in males. Males and androgenized females both showed a preference for the female teaser that was abolished by the 5-HT₂ agonist, DOI. These results point out that 5-HT₂ activity selectively suppresses heterosexual preference induced in the presence of neonatal testosterone. DOI also reduced both male sexual behavior in males and female sexual behavior in androgenized females. Thus, the 5-HT₂ system antagonizes the action of testosterone in stimulating heterosexual orientation and sexual activity, and this is independent of genetic sex.