The effect of ovariectomy, 17β-estradiol treatment, and progesterone treatment on dopaminergic regulation of prepulse inhibition in adult and adolescent female mice.

Abstract

The aim of the present study was to investigate the role of ovarian hormones on dopaminergic regulation of prepulse inhibition (PPI), a measure of sensorimotor gating deficient in schizophrenia and other psychiatric illnesses. Either in adulthood (11 weeks of age) or adolescence (5 weeks of age), female mice underwent ovariectomy (OVX) and were implanted with 17β-estradiol, progesterone, or a combination of these hormones. All mice were tested in adulthood for the acute effect of the dopamine receptor agonist, apomorphine, on PPI. Apomorphine treatment reduced PPI in intact mice and this effect was blocked after OVX in adulthood. A low dose implant of 17β-estradiol prevented this OVX effect and reinstated apomorphine-induced PPI disruption. Following adolescent OVX, the effect of apomorphine was not altered and it significantly reduced PPI in adulthood. A low dose implant of 17β-estradiol following adolescent OVX effect blocked apomorphine-induced PPI disruption in adulthood. Apomorphine had no effect on PPI in any of the mice treated with the high dose of 17β-estradiol or a combination of low-dose 17β-estradiol and progesterone, irrespective of treatment age, suggesting an antipsychotic action. Apomorphine tended to disrupt PPI in mice treated with progesterone only, irrespective of age of OVX. These results suggest that in adult mice, circulating 17β-estradiol and progesterone play an important role in dopaminergic regulation of PPI. This role may develop during adolescence as similar effects of OVX and ovarian hormones were not observed following interventions in 5-week old mice. Our results also confirm and extend previous evidence that 17β-estradiol may have antipsychotic properties.