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.
Highlights
Men and women show different rates of diagnosis, symptomology, and treatment responsivity in most brain disorders
Goal-directed behavior often requires balancing reward seeking with punishment avoidance
We modelled this by adding a component of probabilistic punishment to a reward-seeking task (Fig. 1A), such that reward delivery was paired with a varying chance of foot shock
Summary
Men and women show different rates of diagnosis, symptomology, and treatment responsivity in most brain disorders. Major depressive disorder (MDD) and anxiety disorders are more common in women (Cyranowski, Frank, Young, & Shear, 2000). These patterns suggest that biological sex differences may underlie the disparities in vulnerability to these illnesses. Studies have shown that patients with depressive disorders (Pizzagalli et al, 2009), schizophrenia (Juckel, 2016; Kirsch, Ronshausen, Mier, & Gallhofer, 2007; Schlagenhauf et al, 2008), as well as ADHD (Scheres, Milham, Knutson, & Castellanos, 2007; Strohle et al, 2008) have modified brain responses to reward. Major depression is associated with both a hyposensitivity to rewarding stimuli and hypersensitivity to punishment, and associated imaging findings show attenuated striatal and VTA signals are correlated with increasing frequency of depressive episodes (Kumar et al, 2018)
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