Ovariectomy reverses maternal immune activation-induced deficits in dopamine and NMDA receptor-mediated regulation of prepulse inhibition in female Long-Evans rats

We studied the role of ovarian steroid hormones in the poly(I:C) maternal immune activation model of schizophrenia in rats. Pregnant Long-Evans rats were injected IV with 4 mg/kg of poly(I:C) on gestational day 15. In adult female offspring, we measured prepulse inhibition (PPI) and its disruption by acute treatment with the dopamine receptor agonist, apomorphine (APO), and the NMDA receptor antagonist, MK-801, and compared intact controls and intact poly(I:C) offspring with ovariectomised (OVX) controls and OVX poly(I:C) offspring. PPI was significantly reduced at baseline in intact poly(I:C) rats and the disruption of PPI caused by APO and MK-801 was diminished. Similar effects were observed following OVX in control rats. In contrast, following OVX in poly(I:C) rats, baseline PPI was similar to that found in intact controls and APO and MK-801 significantly reduced PPI in these animals. These results show that OVX reverses the effects of maternal immune activation on PPI and its regulation by dopamine and NMDA receptors. It is likely that the effect of maternal immune activation on PPI regulation involves a delicate endocrine imbalance, most likely involving altered ovarian steroid hormones levels, the effect of which may be reversed by OVX. These results expand our insight into the possible mechanism of action of novel steroid hormone compounds currently trialled for schizophrenia.