Posttraumatic stress disorder (
PTSD) has been associated with abnormal regulation of the hypothalamic-pituitary-adrenal gland axis (HPA). Women demonstrate a more robust HPA response and are twice as likely to develop
PTSD than men. The role of
sex hormones in
PTSD remains unclear. We investigated whether post-
trauma chronic treatment with the
GABA-ergic agent
tiagabine and
dopamine-mimetic
pramipexole affected the behavioral outcome and plasma levels of
corticosterone,
testosterone, or 17β-estradiol in female and male mice. These medications were investigated due to their potential capacity to restore
GABA-ergic and dopaminergic deficits in
PTSD. Animals were exposed to a single prolonged stress procedure (mSPS). Following 13 days treatment with
tiagabine (10 mg/kg) or
pramipexole (1 mg/kg) once daily, the
PTSD-like phenotype was examined in the fear conditioning paradigm. Plasma
hormones were measured almost immediately following the conditioned fear assessment. We report that the exposure to mSPS equally enhanced conditioned fear in both sexes. However, while males demonstrated decreased plasma
corticosterone, its increase was observed in females.
Trauma elevated plasma
testosterone in both sexes, but it had no significant effects on 17β-estradiol. Behavioral manifestation of
trauma was reduced by
pramipexole in both sexes and by
tiagabine in females only. While neither compound affected
corticosterone in stressed animals,
testosterone levels were further enhanced by
tiagabine in females. This study shows sex-dependent efficacy of
tiagabine but not
pramipexole in a mouse model of
PTSD-like symptoms and a failure of
steroid hormones' levels to predict
PTSD treatment efficacy.