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Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats.
Schizophr Res. 2015 Nov; 168(3):634-9.SR

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.

CONCLUSION

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+Show Affiliations

Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: andrea.gogos@florey.edu.au.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.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25979306

Citation

Gogos, Andrea, and Maarten van den Buuse. "Comparing the Effects of 17β-oestradiol and the Selective Oestrogen Receptor Modulators, Raloxifene and Tamoxifen, On Prepulse Inhibition in Female Rats." Schizophrenia Research, vol. 168, no. 3, 2015, pp. 634-9.
Gogos A, van den Buuse M. Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats. Schizophr Res. 2015;168(3):634-9.
Gogos, A., & van den Buuse, M. (2015). Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats. Schizophrenia Research, 168(3), 634-9. https://doi.org/10.1016/j.schres.2015.04.029
Gogos A, van den Buuse M. Comparing the Effects of 17β-oestradiol and the Selective Oestrogen Receptor Modulators, Raloxifene and Tamoxifen, On Prepulse Inhibition in Female Rats. Schizophr Res. 2015;168(3):634-9. PubMed PMID: 25979306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparing the effects of 17β-oestradiol and the selective oestrogen receptor modulators, raloxifene and tamoxifen, on prepulse inhibition in female rats. AU - Gogos,Andrea, AU - van den Buuse,Maarten, Y1 - 2015/06/05/ PY - 2014/12/02/received PY - 2015/04/12/revised PY - 2015/04/23/accepted PY - 2015/5/17/entrez PY - 2015/5/17/pubmed PY - 2016/8/4/medline KW - 17β-Estradiol KW - Female rats KW - Prepulse inhibition (PPI) KW - Raloxifene KW - SERMs KW - Tamoxifen SP - 634 EP - 9 JF - Schizophrenia research JO - Schizophr Res VL - 168 IS - 3 N2 - 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. CONCLUSION: 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. SN - 1573-2509 UR - https://www.unboundmedicine.com/medline/citation/25979306/Comparing_the_effects_of_17β_oestradiol_and_the_selective_oestrogen_receptor_modulators_raloxifene_and_tamoxifen_on_prepulse_inhibition_in_female_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0920-9964(15)00224-8 DB - PRIME DP - Unbound Medicine ER -