Dopamine and Stress System Modulation of Sex Differences in Decision Making

Abstract

Maladaptive decision making is associated with several neuropsychiatric disorders, including problem gambling and suicidal behavior. The prevalence of these disorders is higher in men vs women, suggesting gender-dependent regulation of their pathophysiology underpinnings. We assessed sex differences in decision making using the rat version of the Iowa gambling task. Female rats identified the most optimal choice from session 1, whereas male rats from session 5. Male, but not female rats, progressively improved their advantageous option responding and surpassed females. Estrus cycle phase did not affect decision making. To test whether pharmacological manipulations targeting the dopaminergic and stress systems affect decision making in a sex-dependent manner, male and female rats received injections of a dopamine D receptor (DR) antagonist (eticlopride), DR agonist (quinpirole), corticotropin-releasing factor 1 (CRF) antagonist (antalarmin), and α-adrenergic receptor antagonist (yohimbine; used as a pharmacological stressor). Alterations in mRNA levels of DR and CRF were also assessed. Eticlopride decreased advantageous responding in male, but not female rats, whereas quinpirole decreased advantageous responding specifically in females. Yohimbine dose-dependently decreased advantageous responding in female rats, whereas decreased advantageous responding was only observed at higher doses in males. Antalarmin increased optimal choice responding only in female rats. Higher Drd2 and Crhr1 expression in the amygdala were observed in female vs male rats. Higher amygdalar Crhr1 expression was negatively correlated with advantageous responding specifically in females. This study demonstrates the relevance of dopaminergic- and stress-dependent sex differences to maladaptive decision making.

Risk-based Decision Making in Rats: Modulation by Sex and Amphetamine

“…These results are consistent with another a study using another type of risky decision making 20 task in which the risk of larger reward was associated with a negative consequence of footshocks (Orsini et al, 2016). On the other hand, Georgiou et al (2018) used a rat version of the Iowa Gambling Task (IGT) which required subjects are four choices with probability of 90%, 80%, 60% or 50% to receive 1, 2, 3 or 4 pellets of reward respectively, where the punishment was a 'time out' in the form of not receiving a reward for 10, 20, 30 or 40 seconds respectively before the next trial began. Over the course of learning, female rats tended to show a bias towards the most advantageous choice faster than males, whereas once both groups reached asymptotic levels of performance, male rats chose the most advantageous choice more often than females.…”

Sex differences in stress reactivity in arousal and attention systems

“…In contrast, there are data on sex differences in stress regulation of serotonergic and dopaminergic systems; however, these data do not focus on arousal, but rather domains, such as depressive-like behavior and decision making (e.g. [121][122][123][124]). Thus, unlike in the LC, how sex and stress interact to modulate these other systems to regulate arousal has not been thoroughly explored.…”

DRD2/ANKK1 Taq1A but not COMT single nucleotide polymorphisms contribute to the link between temporal impulsivity and obesity in men

“…The lower binding potential in women in the striatum, however, is interpreted as increased dopaminergic tone 56,57 . In male rats, but not in female rats, a DRD2 antagonist eticlopride was previously shown to increase risky choice behaviours 58 . The same study showed a negative association between impulsivity and striatal DRD2 expression in male rats.…”