Male rats with same sex preference show high experimental anxiety and lack of anxiogenic-like effect of fluoxetine in the plus maze test

Homosexual men show a 2-4 higher risk to suffer anxiety in comparison with heterosexuals. It is unknown if biological factors collaborate to increase such incidence. Fluoxetine produces differential brain activation in homosexuals as compared with heterosexuals, suggesting that it may produce a divergent behavioral effect dependant on sex-preference. The first aim was to evaluate experimental anxiety in male rats that show same-sex preference in the elevated plus maze (EPM). The second goal explored the putative differential effect of fluoxetine (10 mg/kg) in male rats with female and same-sex preference in the EPM. To induce same-sex preference males were prenatally treated with letrozole (0.56 μg/kg, 10-20 gestation days), while controls were males prenatally treated with letrozole that retain female-preference or which mothers received oil. In both groups we found animals with male preference, but the proportion was higher in males that prenatally received letrozole (10 vs. 27%). Males with same-sex preference spent less time and showed lower number of entries to the open arms of the EPM than males that prefer females, regardless of the prenatal treatment. In males with female preference, fluoxetine reduced the time spent and number of entries to the open arms that was absent in males with same-sex preference. These data suggest that biological factors contribute to the high levels of anxiety in subjects with same-sex preference and that fluoxetine in men may produce a divergent action depending on sexual orientation.