ERβ-selective SERMs produce mnemonic-enhancing effects in the inhibitory avoidance and water maze tasks

Estradiol (17β-E2) can have mnemonic-enhancing effects; however, its mechanisms for these effects are not well-understood. The present studies examined effects of 17β-E2 and selective estrogen receptor modulators (SERMs) on emotional and spatial memory of female, Long-Evans rats. First, whether or not 17β-E2 has dose-dependent effects on inhibitory avoidance memory was investigated. Only the highest concentration of 17β-E2 examined (10 μg), which produces physiological concentrations of E2, was effective at enhancing inhibitory avoidance memory (Experiment 1). Further studies were designed to elucidate whether SERMs may produce mnemonic effects similar to those of 17β-E2. Compounds utilized were, the ERα-selective SERMs, propyl pyrazole triol (PPT) or 17α-E2, the ERβ-specific SERMs, diarylpropionitrile (DPN) or 7,12-dihydrocoumestan (coumestrol), or vehicle (oil). Post-training administration of 10 μg 17β-E2 or coumestrol enhanced memory in the inhibitory avoidance task compared to vehicle (Experiment 2). Memory in the water maze was enhanced by post-training administration of 17β-E2, coumestrol, or DPN, compared to vehicle (Experiment 3). Co-administration of 17α-E2&DPN enhanced inhibitory avoidance memory similar to that seen following 17β-E2 or coumestrol (Experiment 4). Administration of E2 2 h post-training was not effective at enhancing memory in the inhibitory avoidance or water maze tasks (Experiment 5). Lordosis of rats was enhanced by 17β-E2, 17α-E2, or PPT, compared to vehicle (Experiment 6). These data suggest that: E2’s actions at ERβ, rather than ERα, may enhance spatial memory, E2’s actions at ERα can facilitate sexual behavior, and that E2’s actions involving both ERα and ERβ may be important for emotional memory.