title: Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats.
abstract: BACKGROUND
  Evidence suggests that oestrogen plays a protective role against the development and severity of schizophrenia. However, while oestrogen may be beneficial as a treatment in schizophrenia, its chronic use is associated with side-effects. Selective oestrogen receptor modulators (SERMs) may provide an alternative, however little is known about the mechanism underlying their effects in schizophrenia.
  
  
  METHODS
  We investigated the effect of raloxifene and tamoxifen on dopaminergic-induced disruptions of prepulse inhibition (PPI). PPI measures sensorimotor gating and PPI disruptions are considered an endophenotype for schizophrenia. Adult female Sprague-Dawley rats were either intact, ovariectomized (OVX), OVX and 17β-oestradiol-treated, OVX and raloxifene-treated (low or high dose), or OVX and tamoxifen-treated (low or high dose).
  
  
  RESULTS
  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. This PPI disruption was prevented in OVX rats treated with 17β-oestradiol, a high dose of raloxifene or a high dose of tamoxifen. In untreated OVX rats, average PPI was 55% after saline and 34% after 1mg/kg apomorphine treatment, a reduction of 21%. However, oestradiol-treated and raloxifene-treated OVX rats showed only a 7% PPI reduction, and tamoxifen-treated OVX rats had a 4% PPI reduction caused by apomorphine treatment. Startle amplitude was not different between the groups.
  
  
  CONCLUSIONS
  The SERMs, raloxifene and tamoxifen, can prevent dopamine D1/D2 receptor-mediated disruptions of sensorimotor gating, similar to oestradiol. These data lend support for the use of SERMs as a treatment for schizophrenia.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: andrea.gogos@florey.edu.au.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gogos
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia; School of Psychological Science, La Trobe University, Bundoora, VIC 3086, Australia.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D065808:Prepulse Inhibition / Q000187:drug effects* / Q000502:physiology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: C000607792:DRD2 protein, rat; D018491:Dopamine Agonists; D004967:Estrogens; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D001058:Apomorphine
keywords: 17β-Estradiol; Female rats; Prepulse inhibition (PPI); Raloxifene; SERMs; Tamoxifen