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Removal of the ovaries suppresses ethanol drinking and promotes aversion-resistance in C57BL/6J female mice

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Abstract

Rationale

Female rodents consume more ethanol (EtOH) than males and exhibit greater aversion-resistant drinking in some paradigms. Ovarian hormones promote EtOH drinking but the contribution of ovarian hormones to aversion-resistant drinking has not been assessed.

Objectives

We aimed to investigate the role of ovarian hormones to aversion-resistant drinking in female mice in a drinking in the dark (DID) task.

Methods

Female C57BL/6 J mice first underwent an ovariectomy (OVX, n = 16) or sham (SHAM, n = 16) surgery. Four weeks following surgery, mice underwent a DID paradigm where they were given access to water and 15% EtOH 3 h into the dark cycle for up to 4 h across 15 drinking sessions. To assess frontloading behavior, bottles were weighed at 30 min, 2 h, and 4 h. Aversion-resistance was tested by adding escalating concentrations of quinine (0, 100, 250, and 500 µM) to the 15% EtOH bottle on sessions 16 – 19.

Results

Removal of the ovaries reduced EtOH consumption in OVX subjects. When assessing aversion-resistant EtOH drinking, mice with ovarian hormones (SHAM) reduced consumption of 250 and 500 µM quinine in EtOH, while OVX subjects exhibited aversion-resistance at all quinine concentrations. OVX mice had greater frontloading for quinine + EtOH at higher concentrations of quinine.

Conclusions

These results indicate that circulating ovarian hormones may be protective against the development of aversion-resistant EtOH drinking and call for further investigation of the role of ovarian hormones in models of addictive behavior.

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Data Availability

The data supporting the findings of this study will be made available upon reasonable request from the authors.

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Funding

This work was supported by NIH grants R15 AA027915 (AKR) and F99 NS118727 (EAS) and the Department of Psychology at Miami University.

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Authors and Affiliations

  1. Department of Psychology and Center for Neuroscience and Behavior, Miami University, 90 N Patterson Ave, Oxford, OH, 45056, USA

    Elizabeth A. Sneddon, Brianna M. Masters, Haifei Shi & Anna K. Radke

  2. Department of Biology, Miami University, Oxford, OH, USA

    Haifei Shi

Authors
  1. Elizabeth A. Sneddon
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  2. Brianna M. Masters
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  3. Haifei Shi
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  4. Anna K. Radke
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Correspondence to Anna K. Radke.

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Sneddon, E.A., Masters, B.M., Shi, H. et al. Removal of the ovaries suppresses ethanol drinking and promotes aversion-resistance in C57BL/6J female mice. Psychopharmacology 240, 2607–2616 (2023). https://doi.org/10.1007/s00213-023-06456-x

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  • DOI: https://doi.org/10.1007/s00213-023-06456-x

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