The Organizational Role of Testicular Hormones and the Androgen Receptor in Anxiety-Related Behaviors and Sensorimotor Gating in Rats

Perinatal exposure to testosterone (T), which can act upon both the androgen receptor (AR) and, via aromatization of T into estrogens, upon estrogen receptors, organizes many adult behaviors in rodents. We compared behaviors in wild-type (WT) male rats and AR-deficient rats with the testicular feminization mutation (Tfm), which on the day of birth were either gonadectomized (Neo-Gdx) or sham operated. In adulthood, all rats were either gonadectomized or sham operated and implanted with T capsules to equilibrate circulating androgens. In each of four tests of behavior related to anxiety (open field, novel object exposure, light/dark box, and elevated plus maze), Neo-Gdx rats showed decreased indices of anxiety and increased activity compared with rats sham operated on the day of birth, with no differences between WT or Tfm males within treatment groups. These results indicate that testicular hormones act in development to increase adult indices of anxiety and decrease activity in males and that functional ARs are not required for this effect. Acoustic startle response was also reduced by Neo-Gdx, suggesting that postnatal testicular secretions potentiate this behavior as well. Adult corticosterone levels and sensorimotor gating, as measured by prepulse inhibition of the acoustic startle response, were increased by neonatal castration in both WT and Tfm rats. These findings indicate a role of T before adulthood in the organization of anxiety-related behaviors, activity, the hypothalamic-pituitary-adrenal axis, and sensorimotor gating in rats, all of which appears to be AR independent.