Testosterone modulation of anxiety in gonadally-suppressed male rhesus monkeys: A role for gonadotropins?

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2013-03, Vol.104, p.97-104
• Main Authors: Suarez-Jimenez, Benjamin, Gore, Heather E., Hachey, Julie, King, Hanna M., Lacreuse, Agnès
• Format: Article
• Language: English
• Subjects: Androgens; Animals; Anxiety; Anxiety - drug therapy; Anxiety - physiopathology; Behavior, Animal - drug effects; Behavior, Animal - physiology; Emotion; Fear; Fear - drug effects; Fear - physiology; Gonadotropin-Releasing Hormone - agonists; Humans; Leuprolide - administration & dosage; Leuprolide acetate; Luteinizing hormone; Luteinizing Hormone - physiology; Macaca mulatta; Macaque; Male; Sex Characteristics; Testosterone - administration & dosage; Testosterone - analogs & derivatives; Testosterone - physiology
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2013.01.004

Testosterone (T) has repeatedly been shown to have anxiolytic properties in rodents, but findings in primates are more mixed. To examine the effects of exogenous T on anxiety, we tested pharmacologically-castrated adult male rhesus monkeys in a modified version of the Human Intruder Paradigm, which measured defensive responses to an unfamiliar human staring directly at them for 2min. Monkeys were tested at 2week intervals during 4 experimental conditions lasting 4weeks each: at baseline, during treatment with the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (200μg/kg; Lupron phase), during treatment with Lupron+T enanthate (TE, 5mg/kg; TE phase) and during treatment with Lupron+oil vehicle (oil phase). We found that the number of anxious behaviors was lower during periods of low T (Lupron only and Lupron+oil phases) than during the Lupron+TE phase. No change in pacing or watching behavior was observed. Thus, in contrast to rodent data, we found no evidence for anxiolytic properties of T in male rhesus monkeys. Rather, T supplementation restored baseline levels of anxiety in Lupron-treated monkeys. These discrepant findings may be best explained by the low levels of gonadotropins achieved by the GnRH agonist. We suggest that Lupron-induced luteinizing hormone (LH) suppression reduced anxiety and that this effect was abolished by T administration. This interpretation is consistent with the view that T increases emotional reactivity to a potential threat and facilitates adaptive arousal response in face of immediate social challenge. ► Suppression of testosterone (T) by a GnRH agonist lowers anxiety in male rhesus monkeys tested in a 2-min stare condition of the Human Intruder Paradigm; exogenous T restores baseline anxiety levels. ► Reduced LH may underlie the beneficial effects of the GnRH on anxiety. ► T promotes an adaptive arousal response in face of an immediate social threat.