Oestradiol Modulation of Cognition in Adult Female Marmosets (Callithrix jacchus)

Abstract

The common marmoset (Callithrix jacchus) provides many advantages over traditional rodent and macaque species as a model for human ageing and may be very useful for studying the effects of sex steroids on cognitive and brain ageing. We present the first study examining the effects of oestrogens on cognitive function in female marmosets. Adult monkeys (3-5 years of age) were trained to a specific learning criterion on a battery of cognitive tasks preoperatively (object discrimination, delayed response with increasing delays and detour reaching with opaque box) and were tested on different versions of these tasks (object reversals, delayed response with randomised delays and detour reaching with clear box) after ovariectomy and simultaneous implantation with 17β-oestradiol (E2 ) (n = 6) or blank (n = 6) Silastic capsules. Acquisition of a delayed matching-to-position task with a 1-s delay was also administered after completion of these tests. E2 -treated monkeys were significantly impaired on the second reversal and showed an increase in perseverative responding from reversals 1-3. Their performance also tended to be worse than that of control monkeys on the delayed response task. Performance acquisition on the delayed matching-to-position tended to be better in E2 -treated relative to control monkeys, although the group difference did not reach statistical significance. No effect of treatment was detected for detour reaching or affiliative behaviours. Overall, the findings indicate that E2 compromises performance on prefrontally-mediated tasks. The suggestion that E2 may improve acquisition on tasks dependent on the hippocampus will require further validation. These results are discussed in the context of dopaminergic and serotonergic signalling. We conclude that the marmoset is a useful new primate model for examining the effects of oestrogens on cognitive function.