Effects of the phytoestrogen coumestrol on locomotor and fear-related behaviors in female mice

Effects of the estrogenic plant isoflavonoid coumestrol (COUM) on locomotor activity and fear-related behaviors in both the absence and the presence o f estradiol benzoate (EB) were examined in adult ovariectomized Swiss-Webst er mice. In a running wheel paradigm conducted over 10 days, with treatment beginning 12 days prior to testing, daily subcutaneous (sc) injections of 10 mug of COUM did not influence locomotor activity, whereas even the low d ose of EB supplied by sc Silastic implant (2.5 mug lasting 5 weeks) produce d a significant increase in locomotor activity over animals receiving vehic le alone. In animals receiving both COUM and EB, locomotor activity was sig nificantly diminished compared to the activity observed in animals receivin g EB alone. The same animals were also tested in three behavioral paradigms having known activity and fear components (open field, dark/light transiti on, elevated plus-maze). COUM did not produce significant effects in these assays. However, in an associative fear learning paradigm (fear conditionin g), COUM produced significantly less freezing ("fearfulness") in the condit ioned fear task than with animals receiving vehicle or a low dose of EB, wh ich did not differ from each other. Unlike EB, which has comparable affinit ies for estrogen receptor (ER) alpha and ER beta, COUM has a higher affinit y for ER beta than for ER alpha. COUM might disrupt estrogen-enhanced locom otor activity by altering the dynamic by which EB acts on the brain through these two ER isoforms. The conditioned fear result suggests that COUM may produce additional effects through alternative pathways. (C) 2001 Academic Press.