title: The role of estrogen and testosterone in female rats in behavioral models of relevance to schizophrenia.
abstract: BACKGROUND
  The sex steroid hormone, estrogen, may play a protective role in schizophrenia. We previously found that estrogen treatment inhibited serotonin-1A (5-HT(1A)) and dopamine D(2) receptor-mediated disruptions of prepulse inhibition (PPI), a measure of sensorimotor gating which is deficient in schizophrenia.
  
  
  OBJECTIVE
  The present study aimed to further explore the role of sex steroid hormones in schizophrenia. Part 1 of this study examined whether estrogen could inhibit PPI disruption induced by the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801. Part 2 investigated whether the functionally protective effect of estrogen occurs in another animal model of schizophrenia, amphetamine-induced locomotor hyperactivity. Part 3 compared our previous PPI findings in estrogen-treated rats, to treatment with testosterone.
  
  
  METHODS
  Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants filled with either a low (E20) or high dose (E100) of estradiol, or a low (T5) or high dose (T20) of testosterone, for at least 2 weeks before behavioral testing.
  
  
  RESULTS
  The disruption of PPI caused by MK-801 (0.1 mg/kg) was significantly reduced by treatment with estradiol (E20 and E100). However, estradiol treatment did not alter amphetamine-induced (0.25 and 0.5 mg/kg) locomotor hyperactivity, in terms of distance traveled, ambulation, or vertical counts. In contrast to estrogen, testosterone treatment did not affect disruption of PPI after administration of 8-OH-DPAT (0.5 mg/kg) or apomorphine (0.3 mg/kg). Testosterone treatment significantly enhanced the MK-801-induced (0.1 mg/kg) PPI disruption.
  
  
  CONCLUSIONS
  Estrogen is functionally protective against 5-HT(1A)-, dopamine D(2)-, and NMDA receptor-induced PPI disruptions, while testosterone treatment enhances NMDA receptor-mediated PPI disruptions.
authors.affiliation: Behavioural Neuroscience Laboratory, The Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia. agogos@mhri.edu.au
authors.forename: Andrea
authors.initials: A
authors.lastname: Gogos
authors.forename: Perrin
authors.initials: P
authors.lastname: Kwek
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity; D000818:Animals; D016291:Dizocilpine Maleate / Q000633:toxicity; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D005260:Female; D010052:Ovariectomy; D011595:Psychomotor Agitation / Q000503:physiopathology / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013739:Testosterone / Q000633:toxicity*
chemical_list: D004967:Estrogens; D013739:Testosterone; D016291:Dizocilpine Maleate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin