The impact of Yohimbine-induced arousal on facets of behavioural impulsivity

Rationale State-dependent changes in physiological arousal may influence impulsive behaviours. Objectives To examine the relationship between arousal and impulsivity, we assessed the effects of yohimbine (an α2-adrenergic receptor antagonist, which increases physiological arousal via noradrenaline release) on performance on established laboratory-based impulsivity measures in healthy volunteers. Methods Forty-three participants received a single dose of either yohimbine hydrochloride or placebo before completing a battery of impulsivity measures. Blood pressure and heart rate were monitored throughout the study. Results Participants in the yohimbine group showed higher blood pressure and better response inhibition in the Stop Signal Task, relative to the placebo group. Additionally, individual changes in blood pressure were associated with performance on Delay Discounting and Information Sampling tasks: raised blood pressure following drug ingestion was associated with more far-sighted decisions in the Delay Discounting Task (lower temporal impulsivity) yet reduced information gathering in the Information Sampling Task (increased reflection impulsivity). Conclusions These results support the notion that impulsive behaviour is dependent upon state physiological arousal; however, distinct facets of impulsivity are differentially affected by physiological changes. Electronic supplementary material The online version of this article (10.1007/s00213-018-5160-9) contains supplementary material, which is available to authorized users.


Supplementary Results and Discussion
We performed an additional set of analyses exploring sex differences in trait, physiological and behavioural measures. We report these analyses as they may be of interest for planning future experiments; however, we caution the readers against driving strong conclusions from these results as our study was not designed to examine sex differences in yohimbine-induced changes in impulsive behaviours and, therefore, is underpowered for this purpose.
To compare male and female participants on demographics, trait and physiological measures, independent samples t-test were performed. Overall, males and females showed no differences in any of the trait measures (Table A1). Males, however, were heavier and taller than females and showed elevated systolic blood pressure at baseline, relative to female participants (see Table A1 for details).
For behavioural data analysis, we employed 2 (Placebo vs Yohimbine) x 2 (Males vs Females) ANOVAs. As an exception, for analysis of the Affective Stop Signal Task (ASST) data, mixed ANOVA with emotion condition (neutral vs fearful) as a within-subject factor was employed. Descriptive statistics of behavioural variables is presented in Table A2.

ASST
The analysis of the stop signal reaction time (SSRT) revealed a three-way (Emotion x Group x Sex) interaction [F(1,34) = 4.45, p = .042, np 2 = 0.12; the interaction is also approaching significance when controlling for drug manipulation group differences in sensation seeking: F(1,33) = 3.91, p = .057, np 2 = 0.11]. Post-hoc repeated measures ANOVA, indicated that response inhibition in males, but not females, was differentially affected by emotional context depending on the drug manipulation (for details see Table A3). Specifically, males showed lower inhibitory control (higher SSRTs) in the fearful relative to the neutral context under placebo (the effect approaching significance following the Bonferroni correction for multiple comparisons α ≤ .025); however, this effect was not present under yohimbine. There were no other significant effects or interactions (see Table A3 and Fig. A1 for details). Together, these results suggest that males were more affected by the task-irrelevant emotional context than females under placebo; however, these effects disappear under the influence of yohimbine.
The previous study by Schwabe et al. (2013) indicated that yohimbine induces opposite effects on fearfulness ratings of fearful facial expressions in males and females: Increasing fearfulness ratings in females while decreasing them in males, with no effect on neutral facial expressions ratings. These behavioural effects were related to enhanced amygdala activity for fearful faces in women, but decreased activity in men. Although we did not find an effect of yohimbine on response inhibition in females, our findings suggest that males might be less reactive to task-irrelevant emotional context under the influence of yohimbine than placebo, partially corroborating findings by Schwabe and colleagues. Overall, these findings corroborate the past literature suggesting that males present higher temporal impulsivity than females (Silverman 2003;Herman et al. 2018).

MCQ
There were no significant main effects or an interaction effect related to the performance on the Probability Discounting and Information Sampling Task (F's < 1.92, p's > .17, np 2 's < 0.05), indicating that there were no sex differences in the performance on the task and that pharmacological manipulation did not affect the performance differently in males and females. 5