title: Testosterone modulation of anxiety in gonadally-suppressed male rhesus monkeys: a role for gonadotropins?
abstract: 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 2 min. Monkeys were tested at 2 week intervals during 4 experimental conditions lasting 4 weeks each: at baseline, during treatment with the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (200 μg/kg; Lupron phase), during treatment with Lupron+T enanthate (TE, 5 mg/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.
authors: Department of Psychology, University of Massachusetts, Amherst MA 01003, USA.
authors: Benjamin
authors: B
authors: Suarez-Jimenez
authors: Heather E
authors: HE
authors: Gore
authors: Julie
authors: J
authors: Hachey
authors: Hanna M
authors: HM
authors: King
authors: Agnès
authors: A
authors: Lacreuse
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000502:physiology; D008253:Macaca mulatta; D008297:Male; D012727:Sex Characteristics; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000502:physiology*
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D016729:Leuprolide