1. Nipissing University, North Bay, ON, Canada; 2. Wayne State University, Detroit, MI, USA; 3. Duke University, Durhma, NC, USA
A wealth of data indicates that a single administration of testosterone modulates various physiological, psychological and behavioural processes related to dominance behaviour (see Bos et al., 2012 for review). Notably, one major limitation of this work is that it has been performed exclusively in women. Here, we developed a novel pharmacological challenge protocol to investigate the effect of testosterone on threat-related neural function in healthy young men. In a placebo-controlled, double-blind crossover design, men (n = 16) first received a GnRH antagonist (Cetrotide Acetate, 3mg) to suppress and reduce variability in baseline testosterone concentrations and then received 100 mg testosterone gel (or placebo). Ninety minutes after testosterone (or placebo) administration, participants performed a well-validated emotional face-processing task (Hariri et al., 2002) during functional magnetic resonance imaging (fMRI). Blood was drawn every 15 minutes after drug administration to track changes in testosterone, SHBG, and estradiol. Results indicated that the GnRH antagonist produced a large decrease in testosterone concentrations (within the hypogonadal range) and testosterone gel administration rapidly (within 30 minutes) increased testosterone concentrations. The imaging results indicated that testosterone modulated threat-related neural function. In particular, testosterone increased centromedial amygdala, hypothalamic, and periaqueductual grey (PAG) reactivity to angry faces. These findings indicate that acute changes in testosterone rapidly modulate the neural circuitry underlying reactive aggression. Our current research is now utilizing this pharmacological challenge protocol to probe the role of testosterone in mediating complex human social behavior (e.g., aggression, risk-taking).