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Research ArticleBEHAVIORAL PHARMACOLOGY

Estrogen Treatment Blocks 8-Hydroxy-2-dipropylaminotetralin- and Apomorphine-Induced Disruptions of Prepulse Inhibition: Involvement of Dopamine D1 or D2 or Serotonin 5-HT1A, 5-HT2A, or 5-HT7 Receptors

Andrea Gogos, Perrin Kwek, Carolina Chavez and Maarten van den Buuse
Journal of Pharmacology and Experimental Therapeutics April 2010, 333 (1) 218-227; DOI: https://doi.org/10.1124/jpet.109.162123
Andrea Gogos
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Victoria, Australia (A.G., P.K., C.C., M.v.d.B.); Centre for Neuroscience, University of Melbourne, Victoria, Australia (A.G.); and Department of Pharmacology, University of Melbourne, Victoria, Australia (C.C., M.v.d.B.)
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Perrin Kwek
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Victoria, Australia (A.G., P.K., C.C., M.v.d.B.); Centre for Neuroscience, University of Melbourne, Victoria, Australia (A.G.); and Department of Pharmacology, University of Melbourne, Victoria, Australia (C.C., M.v.d.B.)
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Carolina Chavez
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Victoria, Australia (A.G., P.K., C.C., M.v.d.B.); Centre for Neuroscience, University of Melbourne, Victoria, Australia (A.G.); and Department of Pharmacology, University of Melbourne, Victoria, Australia (C.C., M.v.d.B.)
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Maarten van den Buuse
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Victoria, Australia (A.G., P.K., C.C., M.v.d.B.); Centre for Neuroscience, University of Melbourne, Victoria, Australia (A.G.); and Department of Pharmacology, University of Melbourne, Victoria, Australia (C.C., M.v.d.B.)
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Abstract

Prepulse inhibition (PPI) is a measure of sensorimotor gating and an endophenotype of schizophrenia. We have shown previously in rats that estrogen treatment prevents disruption of PPI by the 5-HT1A/5-HT7 receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The aim of the present study was to examine the role of dopamine D1 and D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors in these effects. Part 1 of this study investigated the ability of estrogen treatment to reverse PPI disruption induced by 8-OH-DPAT or the dopamine D1/D2 receptor agonist apomorphine. Part 2 of this study compared these effects to the ability of various antagonists in reversing the action of 8-OH-DPAT and apomorphine on PPI. Female Sprague-Dawley rats were ovariectomized (OVX), and, where appropriate, they received silastic implants containing either a low (E20) or high dose (E100) of estrogen. Two weeks later, PPI was assessed using automated startle boxes. The disruption of PPI by either treatment with 8-OH-DPAT (0.5 mg/kg) or apomorphine (0.3 mg/kg) was similarly prevented by E100 treatment. 8-OH-DPAT-induced PPI disruption was reversed by pretreatment with the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg) and the typical antipsychotic and dopamine D2 receptor antagonist haloperidol (0.25 mg/kg), but it was not reversed by pretreatment with the dopamine D1 receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.1 mg/kg), the 5-HT2A/2C receptor antagonist ketanserin (2 mg/kg), or the 5-HT7 receptor antagonist SB-269970 (10 mg/kg). Apomorphine-induced disruptions of PPI were reversed by haloperidol and SCH 23390 only. Estrogen may prevent disruptions of PPI induced by both 8-OH-DPAT and apomorphine by an action on dopamine D2 receptors downstream of 5-HT1A receptors.

Footnotes

    • Received September 30, 2009.
    • Accepted December 29, 2009.
  • This study was funded by the National Health and Medical Research Council of Australia [Grant ID 509234], a Peter Doherty Fellowship [ID 435690] (to A.G.), and a senior research fellowship [ID 435500] (to M.v.d.B.); the J. and P. Clemenger Trust; and the Operational Infrastructure Support from the Victorian State Government.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.162123.

  • ABBREVIATIONS:

    PPI
    prepulse inhibition
    D
    dopamine
    5-HT
    5-hydroxytryptamine (serotonin)
    8-OH-DPAT
    8-hydroxy-2-dipropylaminotetralin
    WAY 100,635
    N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt
    SB-269970
    (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride
    SCH 23390
    R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride
    OVX
    ovariectomized
    E20
    5-mm silastic implant containing 20% estradiol
    E100
    5-mm silastic implant containing 100% estradiol
    ANOVA
    analysis of variance
    BW
    body weight.

  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 376 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 376, Issue 3
1 Mar 2021
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Estrogen Treatment Blocks 8-Hydroxy-2-dipropylaminotetralin- and Apomorphine-Induced Disruptions of Prepulse Inhibition: Involvement of Dopamine D1 or D2 or Serotonin 5-HT1A, 5-HT2A, or 5-HT7 Receptors
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Research ArticleBEHAVIORAL PHARMACOLOGY

Estrogen Treatment Blocks 8-Hydroxy-2-dipropylaminotetralin- and Apomorphine-Induced Disruptions of Prepulse Inhibition: Involvement of Dopamine D1 or D2 or Serotonin 5-HT1A, 5-HT2A, or 5-HT7 Receptors

Andrea Gogos, Perrin Kwek, Carolina Chavez and Maarten van den Buuse
Journal of Pharmacology and Experimental Therapeutics April 1, 2010, 333 (1) 218-227; DOI: https://doi.org/10.1124/jpet.109.162123

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Research ArticleBEHAVIORAL PHARMACOLOGY

Estrogen Treatment Blocks 8-Hydroxy-2-dipropylaminotetralin- and Apomorphine-Induced Disruptions of Prepulse Inhibition: Involvement of Dopamine D1 or D2 or Serotonin 5-HT1A, 5-HT2A, or 5-HT7 Receptors

Andrea Gogos, Perrin Kwek, Carolina Chavez and Maarten van den Buuse
Journal of Pharmacology and Experimental Therapeutics April 1, 2010, 333 (1) 218-227; DOI: https://doi.org/10.1124/jpet.109.162123
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