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

Psychopharmacology (Berl). 2023 Dec;240(12):2607-2616. doi: 10.1007/s00213-023-06456-x. Epub 2023 Aug 31.

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.

Keywords: Alcohol consumption; Aversion-resistant; Drinking in the dark; Ethanol; Female; Frontloading; Mouse; Ovarian hormones; Preference; Quinine.

MeSH terms

  • Alcohol Drinking
  • Animals
  • Ethanol / pharmacology
  • Female
  • Hormones
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ovary*
  • Quinine*

Substances

  • Quinine
  • Ethanol
  • Hormones