Sex and the Lab: An Alcohol‐Focused Commentary on the NIH Initiative to Balance Sex in Cell and Animal Studies

Abstract

Background In May 2014, Dr. Francis Collins, the director of US National Institutes of Health, and Dr. Janine Clayton, the director of the US National Institutes of Health Office of Research on Women’s Health (ORWH) published a commentary in the journal Nature announcing new policies to ensure that preclinical research funded by the NIH consider both males and females. While these policies are still developing, they have already generated great interest by the scientific community and triggered both criticism and applause. This review provides a description and interpretation of the NIH guidelines and it traces the history that led to their implementation. As expected, this NIH initiative generated some anxiety in the scientific community. The use of female animals in the investigation of basic mechanisms is perceived to increase variability in the results, and the use of both sexes has been claimed to slow the pace of scientific discoveries and to increase the cost at a time characterized by declining research support. Purpose This review discusses issues related to the study of sex as a biological variable in alcohol studies and provides examples of how researchers have successfully addressed some of them. A practical strategy is provided to include both sexes in biomedical research while maintaining control of the research direction. Conclusion The inclusion of sex as an important biological variable in experimental design, analysis and reporting of preclinical alcohol research is likely to lead to a better understanding of alcohol pharmacology and the development of alcohol use disorder, may promote drug discovery for new pharmacotherapies by increasing scientific rigor, and may provide clinical benefit to women’s health. This review aims to promote the understanding of the NIH sex as biological variable guidelines and to provide alcohol researchers with a theoretical and practical framework for working with both sexes in preclinical research.

Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking

“…A related issue is that behavioral neuroscience has historically largely used male rodents based on the assumption that females would introduce greater day-to-day variability due to hormonal effects across their estrous cycle (McCarthy, 2015 ; Guizzetti et al, 2016 ). Thus, it is possible that the present study “missed” effects of nicotine due to hormone-related variability in female self-administration.…”

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“…Considering these sex differences observed in clinical populations, strikingly few preclinical animal studies of alcohol use have directly compared males and females (Becker et al 2011; Becker and Koob 2016; Beery and Zucker 2011; Guizzetti et al 2016; Priddy et al 2017). This has traditionally been related to concerns about variability related to hormones and estrous cycle in females.…”

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“…Among the scientific community there is an increased need for including sex as a biological variable [27][28][29]. Interestingly, the effect of sex in kidney disease and RAS has recently become the focus of many investigators [30].…”