Effects of testosterone on cognition in young adult male rhesus monkeys

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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.

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