Endocrine disruption and cognitive function in adolescent female rhesus monkeys

Female rhesus monkeys (n=8/group) received daily oral doses of exogenous estrogen [diethylstilbestrol (DES), 0.5 mg/kg, methoxychlor (MXC), 25 or 50 mg/kg] for 6 months before and after the anticipated age of menarche. Behavior was assessed during and for 9 months after dosing. Visual discrimination performance (simultaneous nonmatch-to-sample with trial-unique stimuli) conducted during dosing demonstrated delayed improvement and poorer performance in the MXC50 group, with some similar effects in the DES group. Visual recognition memory, assessed with delays of < or = 3 s, was not apparently affected. Spatial working memory, assessed after dosing, also showed acquisition deficits and possible working memory difficulties in the MXC50 group. Spontaneous motor activity, monitored at 6-month intervals, was not affected by treatment. Late peak latencies of the auditory brainstem response (ABR) were shorter in the DES group 6 months after treatment, suggesting long-term effects on brain. The study suggests that some aspects of brain function can be modified by exposure to exogenous estrogen during pubertal development. Although DES is a more potent estrogen, the high-dose MXC group was more affected behaviorally. Differential effects of the two agents at the estrogen receptor subtypes (ER alpha and ER beta) may be relevant to the differential behavioral outcomes.