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The role of estrogen and testosterone in female rats in behavioral models of relevance to schizophrenia

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Abstract

Rationale

The sex steroid hormone, estrogen, may play a protective role in schizophrenia. We previously found that estrogen treatment inhibited serotonin-1A (5-HT1A) and dopamine D2 receptor-mediated disruptions of prepulse inhibition (PPI), a measure of sensorimotor gating which is deficient in schizophrenia.

Objectives

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-HT1A-, dopamine D2-, and NMDA receptor-induced PPI disruptions, while testosterone treatment enhances NMDA receptor-mediated PPI disruptions.

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Acknowledgments

Funding for this study was provided by the National Health and Medical Research Council of Australia in the form of a Project Grant (ID 509234), a Peter Doherty Fellowship (ID 435690 to AG), and a senior research fellowship (ID 435500 to MvdB); the J. & P. Clemenger Trust; and the Operational Infrastructure Support (OIS) from the Victorian State Government. All experiments in this study were in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes (1990) set out by the National Health and Medical Research Council of Australia. There are no conflicts of interest to report.

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Authors and Affiliations

  1. Behavioural Neuroscience Laboratory, The Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria, 3052, Australia

    Andrea Gogos, Perrin Kwek & Maarten van den Buuse

  2. Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia

    Andrea Gogos

  3. Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia

    Maarten van den Buuse

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  1. Andrea Gogos
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  2. Perrin Kwek
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Correspondence to Andrea Gogos.

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Gogos, A., Kwek, P. & van den Buuse, M. The role of estrogen and testosterone in female rats in behavioral models of relevance to schizophrenia. Psychopharmacology 219, 213–224 (2012). https://doi.org/10.1007/s00213-011-2389-y

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  • DOI: https://doi.org/10.1007/s00213-011-2389-y

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