RESUMEN
Animal studies indicate that sex hormones have widespread effects on the brain, cognition and emotion, but findings in humans are inconsistent. Well-controlled studies in nonhuman primates are crucial to resolve these discrepancies. In this study, we examined the effects of testosterone (T) on emotion in male rhesus monkeys. Six young adult males were tested on two emotional tasks during three hormonal conditions in a crossover design: when intact at baseline and when pharmacologically hypogonadal with add-back of T or placebo. The emotional tasks were the Approach-Avoidance task, which tested behavioral responses to three categories of objects (familiar, novel, and negative) and a Social Playback task which tested behavioral responses to scenes of unfamiliar conspecifics engaged in three types of social activities (neutral, positive, or negative). Following a 4-week baseline period, monkeys were treated with Depot Lupron, 200µg/kg before being randomly assigned to one of two treatment groups: Depot Lupron+Testosterone Enanthate (TE, 20mg/kg) or Depot Lupron+oil vehicle. In each treatment group, monkeys received one injection of Lupron and one injection of TE or one injection of Lupron and one injection of oil at the onset of a 4-week testing period, before crossing over to the alternate treatment for an additional 4weeks of testing. TE treatment had no effect on behavioral measures in the Approach-Avoidance task. For the Social Playback task, however, TE significantly increased watching time of video clips which depicted fights between unfamiliar conspecifics. The enhancing effect of T on watching time for negative social scenes is consistent with human data suggesting that T decreases aversion or facilitates approach to threatening social stimuli. Further studies are needed to understand the mechanisms by which T may mediate responsiveness to social threat in male primates.
Asunto(s)
Atención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Miedo/efectos de los fármacos , Macaca mulatta/fisiología , Testosterona/farmacología , Algoritmos , Animales , Atención/fisiología , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Conducta Animal/fisiología , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Emociones/efectos de los fármacos , Emociones/fisiología , Miedo/fisiología , Hormona Liberadora de Gonadotropina/agonistas , Leuprolida/administración & dosificación , Leuprolida/farmacología , Masculino , Distribución Aleatoria , Conducta Social , Testosterona/administración & dosificaciónRESUMEN
The relationships between testosterone (T) and cognitive function remain unclear. In men, associations between endogenous T levels and cognitive performance have not consistently been found and the effects of T treatment on cognition remain ambiguous: several studies have reported beneficial effects of T administration on cognitive function, but recent data indicate no effect or even detrimental effects of T. Studies in nonhuman primates may help resolve these discrepancies. We conducted the first study examining the activational effects of T on cognition in adult male nonhuman primates. Six young adult male rhesus monkeys (5-6 years old) were tested for 16 weeks on a battery of 4 memory tasks (1) when intact at baseline (winter); (2) when hypogonadal with add-back of T or placebo in a double blind cross-over design and (3) when intact following wash-out (summer phase). The cognitive tasks consisted of the Delayed Non-Matching-To-Sample (DNMS) with mixed delays, the spatial-Delayed Recognition Span Test (spatial-DRST) and the Delayed Response (DR) task. Following a 4-week baseline period, monkeys were treated with a gonadotropin releasing hormone (GnRH) agonist (Depot Lupron, 200 microg/kg) before being randomly assigned to one of 2 treatment groups: Lupron+testosterone enanthate (TE, 20 mg/kg) or Lupron+oil vehicle. In each treatment group, monkeys received Lupron+TE, or Lupron+oil, for 4 weeks before crossing over to the alternate treatment for an additional 4weeks. After a 2 months wash-out period, monkeys were retested on the battery of tasks for an additional 4weeks. T levels did not vary significantly between the winter and summer months of testing, indicating a lack of seasonal effect in these monkeys housed indoors. TE treatment yielded supraphysiological T levels decreasing progressively over 4 weeks. This treatment was associated with impaired recognition memory at the 600s delay of the DNMS, suggesting compromised medial temporal lobe function, but had no effect on DR or spatial-DRST. Further studies are needed to determine whether T may enhance memory in aged male monkeys.