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Tamoxifen disrupts consolidation and retrieval of morphine-associated contextual memory in male mice: interaction with estradiol

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Abstract

Rationale

Tamoxifen (TMX), a selective estrogen receptor modulator, can affect cognitive functions of the brain. The conditioned place preference (CPP) paradigm involves memory for the association between contextual cues and the rewarding properties produced by a drug.

Objectives

The effects of TMX alone and in combination with estradiol (E2) on reward-related memory of morphine were investigated in adult male mice.

Materials and methods

Using an unbiased CPP paradigm, the ability of morphine sulfate (0.5–10 mg/kg, s.c.) to produce CPP was studied. Afterwards, the effects of TMX (1–10 mg/kg, s.c.) on the acquisition, consolidation, and expression of morphine-induced CPP were assessed. We have also evaluated the possible effects of s.c. E2 (10–200 μg/kg) and its co-administration with TMX (10 mg/kg, s.c.) on the consolidation and retrieval of morphine-associated contextual memory.

Results

(1) Morphine (0.5–10 mg/kg) significantly induced CPP in a dose-dependent manner. (2) TMX (10 mg/kg) significantly reduced the time spent by mice in the morphine compartment when given immediately after each conditioning session (consolidation) or 30 min before testing for place preference in the absence of morphine (expression), whereas it had no effect when administered 30 min before each training session (acquisition). (3) Post-training or pre-testing administration of E2 increased morphine-induced CPP in a dose-dependent manner. (4) In addition, concomitant administration of E2 with TMX appears to prevent the impairing effect produced by TMX.

Conclusions

TMX appears to disrupt consolidation and retrieval of morphine-associated contextual memory and this impairing effect might be prevented by E2 treatment.

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Acknowledgments

This study was supported by grant 6446 from the vice-chancellor for research of Tehran University of Medical Sciences to BE. We would like to thank Dr. M. A. Khoshnoodi for his helpful discussions and two anonymous reviewers for their constructive reviews.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Behnaz Esmaeili, Zahra Basseda, Shervin Gholizadeh & Ahmad Reza Dehpour

  2. Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Behnaz Esmaeili, Zahra Basseda, Shervin Gholizadeh & Mehrak Javadi Paydar

  3. Interdisciplinary Neuroscience Research Program (INRP), Tehran University of Medical Sciences, Tehran, Iran

    Behnaz Esmaeili & Zahra Basseda

  4. Brain and Spinal Injury Repair Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Mehrak Javadi Paydar

Authors
  1. Behnaz Esmaeili
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  2. Zahra Basseda
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  3. Shervin Gholizadeh
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  4. Mehrak Javadi Paydar
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  5. Ahmad Reza Dehpour
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Correspondence to Ahmad Reza Dehpour.

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Esmaeili, B., Basseda, Z., Gholizadeh, S. et al. Tamoxifen disrupts consolidation and retrieval of morphine-associated contextual memory in male mice: interaction with estradiol. Psychopharmacology 204, 191–201 (2009). https://doi.org/10.1007/s00213-008-1448-5

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  • DOI: https://doi.org/10.1007/s00213-008-1448-5

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