Sex differences in reward- and punishment-guided actions

Abstract

Differences in the prevalence and presentation of psychiatric illnesses in men and women suggest that neurobiological sex differences confer vulnerability or resilience in these disorders.Rodent behavioral models are critical for understanding the mechanisms of these differences.Reward processing and punishment avoidance are fundamental dimensions of the symptoms of psychiatric disorders. Here we explored sex differences along these dimensions using multiple and distinct behavioral paradigms. We found no sex difference in reward-guided associative learning but a faster punishment-avoidance learning in females. After learning, females were more sensitive than males to probabilistic punishment but less sensitive when punishment could be avoided with certainty. No sex differences were found in reward-guided cognitive flexibility.Thus, sex differences in goal-directed behaviors emerged selectively when there was an aversive context. These differences were critically sensitive to whether the punishment was certain or unpredictable. Our findings with these new paradigms provide conceptual and practical tools for investigating brain mechanisms that account for sex differences in susceptibility to anxiety and impulsivity. They may also provide insight for understanding the evolution of sex-specific optimal behavioral strategies in dynamic environments.

A novel multidimensional reinforcement task in mice elucidates sex-specific behavioral strategies

“…As such, unidimensional behavioral tasks are not sufficient to gain a holistic understanding of behavioral functions. In recent years, research focused on understanding the biological variables contributing to psychiatric disorders has highlighted sex-based differences in the development and presentation of symptoms as well as in fundamental behavioral processes [1][2][3][4]. Understanding the factors contributing to sex-specific vulnerability to neuropsychiatric disease is critical to developing treatments that are safe and effective for both sexes.…”

“…Sex-based differences in reward seeking and avoidance offer an ideal model to explore bias and strategy in a behavioral task while providing insight into the neurobiological basis of information encoding [5][6][7][8][9]. For example, even though females will selfadminister opiates at higher rates than males [2], when given a choice between opiates and a high-fat reward they choose the non-drug reinforcer over the drug alternative at a higher rate than males [10], clearly highlighting that sex differences do not manifest themselves as universal behavioral principles, but rather are a complex interaction between sex and environment.…”