Poster Presentation The International Congress of Neuroendocrinology 2014

Examining the effect of raloxifene and tamoxifen in an animal model of schizophrenia (#133)

Andrea Gogos 1 , Maarten van den Buuse 1 2
  1. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
  2. School of Psychological Science, La Trobe University, Bundoora, VIC, Australia

Evidence suggests that estrogen plays a protective role against the development and severity of schizophrenia. Although estrogen may be beneficial in treating schizophrenia, its chronic use is associated with side-effects. Selective estrogen receptor modulators (SERMs) may provide a better alternative to estrogen and be a safer treatment option for both men and women. Our previous research in rats, suggests that estradiol may protect against schizophrenia symptoms by acting on the dopaminergic system. Therefore, we propose that SERMs can also modulate the dopaminergic system, and that this modulation is the basis for their effects in schizophrenia. We investigated the effect of raloxifene and tamoxifen on dopaminergic-induced disruptions of prepulse inhibition (PPI). PPI is an operational measure of sensorimotor gating; this gating is a normal protective mechanism in the brain functioning to filter irrelevant information, allowing for coherent thought. Adult female Sprague-Dawley rats were either intact, ovariectomised (OVX), OVX and estradiol-treated, OVX and raloxifene-treated, OVX and tamoxifen-treated. The dopamine D1/D2 receptor agonist, apomorphine (0, 0.1, 0.3 and 1mg/kg), caused the expected dose-dependent disruption in PPI in intact and OVX rats. However, this PPI disruption was prevented in OVX rats treated with estradiol, raloxifene or tamoxifen. In untreated OVX rats, average PPI was 55% after saline and 36% after 1mg/kg apomorphine treatment, a reduction of 19%. However, estradiol-treated and raloxifene-treated OVX rats showed only a 7% reduction in PPI, and tamoxifen-treated OVX rats had a 3% reduction in PPI caused by apomorphine treatment. In conclusion, the SERMs, raloxifene and tamoxifen, can prevent dopamine-induced disruptions in sensorimotor gating, similar to estradiol. This data lends support to the hypothesis that estrogen/SERMs play a protective role in schizophrenia via modulation of the dopaminergic system.