Sex differences in behavioral strategies: avoiding interpretational pitfalls
Introduction
Neuroscientists have studied animal behavior in laboratory settings for over a century, leading to an ever-increasing understanding of the relationship between structure, physiology, and function in the mammalian brain. In particular, rodent behavioral models have provided key insights into the neural basis of dozens of complex processes, including learning, decision-making, stress coping, aggression, and substance abuse. However, because the vast majority of behavioral neuroscience research has been conducted in males [1], we inarguably (and regrettably) know much more about the male brain than we do about the female brain. In a recent attempt to rectify this imbalance across biomedical research, the NIH implemented a policy that requires funded researchers to consider sex as a biological variable (SABV) and include subjects of both sexes in all experiments [2]. Despite some resistance [3, 4], this initiative is likely to succeed in illuminating aspects of brain function that are common to both sexes, as well as those that are sexually dimorphic [5]. Information of either kind can be useful to basic and translational scientists alike, but it is critical — especially in behavioral research — that we interpret potential sex differences in outcome measures thoughtfully.
When we conduct behavioral experiments, we are, in essence, asking animals to tell us what the situation we have placed them in means to them. In many cases, the animal might engage any number of responses, and it is up to us to determine what each one means to us. When males and females differ quantitatively in the outcome measures that we have defined, it is important to consider whether these differences reflect true disparities in, for example, cognitive ability or emotional state, or rather a qualitative difference in behavioral strategies, which may optimally serve the potentially discrete needs of each sex. In this review, we discuss recent studies that highlight this distinction, and emphasize the need for thorough, careful behavioral analyses as more neuroscientists begin to incorporate SABV into experimental design.
Section snippets
Sex differences in common behavioral models
How do animals process information about threatening environments and stimuli? Although it is not necessarily surprising to learn that males and females might behave differently in response to stressful events, a nuanced understanding of how and why these differences exist is only just starting to emerge. A recent paper from Tronson and colleagues [6•] nicely demonstrates that after classical context fear conditioning, female mice are more likely than males to show a generalized freezing
Conclusions
The studies discussed here comprise just a small subset of the rapidly growing body of behavioral neuroscience literature that considers sex as a biological variable. Our primary goal was to emphasize the need to be mindful of outcome interpretations and consider alternate explanations for sex differences in common paradigms. As we have argued previously [31], this may be especially important in stress-related and anxiety-related models like the elevated plus maze and forced swim test, which
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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